Il4ra

Summary

Gene Symbol: Il4ra
Description: interleukin 4 receptor, alpha
Alias: CD124, Il4r, interleukin-4 receptor subunit alpha, IL-4 receptor alpha chain, IL-4 receptor subunit alpha, IL-4R subunit alpha, IL-4R-alpha, IL-4RA
Species: mouse
Products:     Il4ra

Top Publications

  1. Radwanska M, Cutler A, Hoving J, Magez S, Holscher C, Bohms A, et al. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection. PLoS Pathog. 2007;3:e68 pubmed
    ..Furthermore, a beneficial role for IL-4Ralpha signaling in L. major infection is revealed in which IL-4/IL-13-responsive non-CD4+ T cells induce protective responses. ..
  2. Munitz A, Brandt E, Mingler M, Finkelman F, Rothenberg M. Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis. Proc Natl Acad Sci U S A. 2008;105:7240-5 pubmed publisher
    ..Taken together, our data provide a comprehensive mechanistic analysis of the critical role by which IL-13Ralpha1 mediates allergic lung pathology and highlight unforeseen roles for the type II IL-4R. ..
  3. Fernandez Botran R, Chilton P, Ma Y, Windsor J, Street N. Control of the production of soluble interleukin-4 receptors: implications in immunoregulation. J Leukoc Biol. 1996;59:499-504 pubmed
  4. Tanaka Y, Hamano S, Gotoh K, Murata Y, Kunisaki Y, Nishikimi A, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2. Nat Immunol. 2007;8:1067-75 pubmed
    ..Thus, Dock2 links T cell receptor signals to downregulation of IL-4Ralpha to control the lineage commitment of CD4+ T cells. ..
  5. Gessner A, Schröppel K, Will A, Enssle K, Lauffer L, Rollinghoff M. Recombinant soluble interleukin-4 (IL-4) receptor acts as an antagonist of IL-4 in murine cutaneous Leishmaniasis. Infect Immun. 1994;62:4112-7 pubmed
    ..These results suggest a therapeutic value of sIL-4R in diseases in which neutralization of IL-4 is desirable. ..
  6. Webb D, Mahalingam S, Cai Y, Matthaei K, Donaldson D, Foster P. Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4Ralpha-independent airway hyperreactivity. Eur J Immunol. 2003;33:3377-85 pubmed
    ..Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice. ..
  7. Shirey K, Cole L, Keegan A, Vogel S. Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism. J Immunol. 2008;181:4159-67 pubmed
    ..Thus, redirection of macrophage differentiation by Ft LVS from a classical to an alternative activation state enables the organism to survive at the expense of the host. ..
  8. Jenkins S, Rückerl D, Thomas G, Hewitson J, Duncan S, Brombacher F, et al. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J Exp Med. 2013;210:2477-91 pubmed publisher
    ..Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment. ..
  9. King I, Mohrs M. IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J Exp Med. 2009;206:1001-7 pubmed publisher
    ..Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo. ..

More Information

Publications81

  1. Shirey K, Pletneva L, Puche A, Keegan A, Prince G, Blanco J, et al. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4R alpha-, TLR4-, and IFN-beta-dependent. Mucosal Immunol. 2010;3:291-300 pubmed publisher
    ..RSV-infected cotton rats treated with a cyclooxygenase-2 inhibitor increased expression of lung AA-M phi. These data suggest new treatment strategies for RSV that promote AA-M phi differentiation. ..
  2. Khodoun M, Lewis C, Lewis C, Yang J, Orekov T, Potter C, et al. Differences in expression, affinity, and function of soluble (s)IL-4Ralpha and sIL-13Ralpha2 suggest opposite effects on allergic responses. J Immunol. 2007;179:6429-38 pubmed
  3. Herbst T, Esser J, Prati M, Kulagin M, Stettler R, Zaiss M, et al. Antibodies and IL-3 support helminth-induced basophil expansion. Proc Natl Acad Sci U S A. 2012;109:14954-9 pubmed publisher
    ..polygyrus bakeri, parasite rejection following challenge infection was impaired. These data reveal a role for isotype-switched antibodies in promoting basophil expansion and effector function following helminth infection. ..
  4. Holscher C, Arendse B, Schwegmann A, Myburgh E, Brombacher F. Impairment of alternative macrophage activation delays cutaneous leishmaniasis in nonhealing BALB/c mice. J Immunol. 2006;176:1115-21 pubmed
    ..Together, these results suggest that alternative macrophage activation contributes to susceptibility in cutaneous leishmaniasis. ..
  5. Masic A, Hurdayal R, Nieuwenhuizen N, Brombacher F, Moll H. Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice. PLoS Negl Trop Dis. 2012;6:e1721 pubmed publisher
    ..We discuss these findings and suggest that the IL4/IL4R? signaling pathway could be a key pathway to trigger when designing vaccines aimed to prevent damaging processes in ..
  6. Ko C, Cuthbert R, Orsi N, Brooke D, Perry S, Markham A, et al. Lack of interleukin-4 receptor alpha chain-dependent signalling promotes azoxymethane-induced colorectal aberrant crypt focus formation in Balb/c mice. J Pathol. 2008;214:603-9 pubmed publisher
  7. Perona Wright G, Mohrs K, Mayer K, Mohrs M. Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo. J Immunol. 2010;184:615-23 pubmed publisher
    ..Together these data reveal a tightly controlled program of changing IL-4 responsiveness that characterizes the initiation, amplification, and restriction of a Th2 response in vivo. ..
  8. Huang Z, Xin J, Coleman J, Huang H. IFN-gamma suppresses STAT6 phosphorylation by inhibiting its recruitment to the IL-4 receptor. J Immunol. 2005;174:1332-7 pubmed
    ..Our results suggest that IFN-gamma may suppress phosphorylation of STAT6 by inhibiting its recruitment to the IL-4R. ..
  9. Ramalingam T, Pesce J, Sheikh F, Cheever A, Mentink Kane M, Wilson M, et al. Unique functions of the type II interleukin 4 receptor identified in mice lacking the interleukin 13 receptor alpha1 chain. Nat Immunol. 2008;9:25-33 pubmed
    ..In contrast to Il4ra-/- mice, which have weak T(H)2 responses, Il13ra1-/- mice had exacerbated T(H)2 responses...
  10. Stenzel W, Muller U, Kohler G, Heppner F, Blessing M, McKenzie A, et al. IL-4/IL-13-dependent alternative activation of macrophages but not microglial cells is associated with uncontrolled cerebral cryptococcosis. Am J Pathol. 2009;174:486-96 pubmed publisher
    ..neoformans. ..
  11. Dewals B, Hoving J, Leeto M, Marillier R, Govender U, Cutler A, et al. IL-4Ralpha responsiveness of non-CD4 T cells contributes to resistance in schistosoma mansoni infection in pan-T cell-specific IL-4Ralpha-deficient mice. Am J Pathol. 2009;175:706-16 pubmed publisher
    ..Here we generated a novel mouse model lacking IL-4Ralpha expression specifically on all T cells (iLck(cre)Il4ra(-/lox)), which was compared with CD4(+) T cell-specific IL-4Ralpha-deficient mice (Lck(cre)Il4ra(-/lox)), to ..
  12. Elgueta R, Sepulveda F, Vilches F, Vargas L, Mora J, Bono M, et al. Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells. J Immunol. 2008;180:6501-7 pubmed
    ..Thus, besides the direct effect of RA on T cell gut tropism, our results show that the induction of a gut-homing phenotype on CD4(+) T cells is also influenced by the effect of IL-4 on gut-associated DC. ..
  13. Zaiss M, Kurowska Stolarska M, Böhm C, Gary R, Scholtysek C, Stolarski B, et al. IL-33 shifts the balance from osteoclast to alternatively activated macrophage differentiation and protects from TNF-alpha-mediated bone loss. J Immunol. 2011;186:6097-105 pubmed publisher
    ..Thus, we show in this study that IL-33 is an important bone-protecting cytokine and may be of therapeutic benefit in treating bone resorption. ..
  14. Herbert D, Holscher C, Mohrs M, Arendse B, Schwegmann A, Radwanska M, et al. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity. 2004;20:623-35 pubmed
    ..Together, this shows that alternative macrophages are essential during schistosomiasis for protection against organ injury through downregulation of egg-induced inflammation. ..
  15. Dickgreber N, Farrand K, van Panhuys N, Knight D, McKee S, Chong M, et al. Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion. J Leukoc Biol. 2012;92:999-1009 pubmed publisher
    ..These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus. ..
  16. Harris D, Goodrich S, Mohrs K, Mohrs M, Lund F. Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor alpha, and Th2 cells. J Immunol. 2005;175:7103-7 pubmed
  17. Pace L, Rizzo S, Palombi C, Brombacher F, Doria G. Cutting edge: IL-4-induced protection of CD4+CD25- Th cells from CD4+CD25+ regulatory T cell-mediated suppression. J Immunol. 2006;176:3900-4 pubmed
    ..These findings support an essential role of IL-4 signaling for CD4(+)CD25(-) Th cell activation and indicate that IL-4-induced proliferation of CD4(+)CD25(+) Treg cells is compatible with their suppressive activity. ..
  18. Potian J, Rafi W, Bhatt K, McBride A, Gause W, Salgame P. Preexisting helminth infection induces inhibition of innate pulmonary anti-tuberculosis defense by engaging the IL-4 receptor pathway. J Exp Med. 2011;208:1863-74 pubmed publisher
    ..The Th2 response can thus enhance the intracellular persistence of Mtb, in part by mediating the alternative activation of macrophages via the IL-4R? signaling pathway...
  19. Egawa M, Mukai K, Yoshikawa S, Iki M, Mukaida N, Kawano Y, et al. Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4. Immunity. 2013;38:570-80 pubmed publisher
    ..Thus, inflammatory monocytes can be converted from being proinflammatory to anti-inflammatory under the influence of basophils in allergic reactions...
  20. Alexander J, Brombacher F, McGachy H, McKenzie A, Walker W, Carter K. An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection. Eur J Immunol. 2002;32:2923-33 pubmed
    ..Collectively our results suggest that IL-4 plays a critical role in early lesion development, and that IL-13 plays a crucial part in maintaining a chronic non-healing infection. ..
  21. Junttila I, Mizukami K, Dickensheets H, Meier Schellersheim M, Yamane H, Donnelly R, et al. Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Ralpha, IL-13Ralpha1, and gammac regulates relative cytokine sensitivity. J Exp Med. 2008;205:2595-608 pubmed publisher
    ..These findings provide an explanation for IL-13's principal function as an "effector" cytokine and IL-4's principal role as an "immunoregulatory" cytokine. ..
  22. Morris S, Heidorn S, Herbert D, Perkins C, Hildeman D, Khodoun M, et al. Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation. J Immunol. 2009;182:1429-38 pubmed
    ..Thus, endogenously produced IL-4 is an important regulator of quantitative as well as qualitative aspects of T cell immunity. ..
  23. Weinreich M, Takada K, Skon C, Reiner S, Jameson S, Hogquist K. KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine production and upregulation of bystander chemokine receptors. Immunity. 2009;31:122-30 pubmed publisher
    ..Our findings support a model where KLF2 regulates T cell trafficking by direct regulation of S1P(1) and CD62L and restrains spontaneous cytokine production in naive T cells. ..
  24. Goh Y, Henderson N, Heredia J, Red Eagle A, Odegaard J, Lehwald N, et al. Eosinophils secrete IL-4 to facilitate liver regeneration. Proc Natl Acad Sci U S A. 2013;110:9914-9 pubmed publisher
    ..Instead, IL-4 exerts its proliferative actions via IL-4R? in hepatocytes. Our findings thus provide a unique mechanism by which eosinophil-derived IL-4 stimulates hepatocyte proliferation in regenerating liver...
  25. Noben Trauth N, Lira R, Nagase H, Paul W, Sacks D. The relative contribution of IL-4 receptor signaling and IL-10 to susceptibility to Leishmania major. J Immunol. 2003;170:5152-8 pubmed
    ..These studies suggest that regardless of parasite substrain, IL-10 is as important as IL-4/IL-13 in promoting susceptibility to L. major and even more so for those substrains that are relatively resistant to IFN-gamma mediated killing. ..
  26. Marsland B, Kurrer M, Reissmann R, Harris N, Kopf M. Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages. Eur J Immunol. 2008;38:479-88 pubmed publisher
    ..Taken together, these data show that lung tissue damage caused by hookworm infection can result in the development of COPD and emphysema...
  27. Muller U, Piehler D, Stenzel W, Kohler G, Frey O, Held J, et al. Lack of IL-4 receptor expression on T helper cells reduces T helper 2 cell polyfunctionality and confers resistance in allergic bronchopulmonary mycosis. Mucosal Immunol. 2012;5:299-310 pubmed publisher
    ..Moreover, the data demonstrate that the quality of the Th2 response has an impact on type 2 inflammation. The analysis of polyfunctional Th2 cells may be useful for monitoring the course of the disease. ..
  28. Seki Y, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, et al. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proc Natl Acad Sci U S A. 2002;99:13003-8 pubmed
    ..Therefore, the induced SOCS5 protein in Th1 differentiation environment may play an important role by regulating Th1 and Th2 balance. ..
  29. Horsnell W, Vira A, Kirstein F, Mearns H, Hoving J, Cutler A, et al. IL-4R?-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunol. 2011;4:83-92 pubmed publisher
    ..Together, these data demonstrate that both IL-4R? and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections. ..
  30. Noben Trauth N, Shultz L, Brombacher F, Urban J, Gu H, Paul W. An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice. Proc Natl Acad Sci U S A. 1997;94:10838-43 pubmed
    ..These results indicate that an IL-4-independent, beta2-microglobulin-dependent pathway exists through which the CD62L-low CD4+ population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells. ..
  31. Barner M, Mohrs M, Brombacher F, Kopf M. Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Curr Biol. 1998;8:669-72 pubmed
    ..Injection of recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2-/- mice. Our results suggest that IL-13 regulates Th2 responses to nematode infection and requires IL-4R alpha. ..
  32. Webb D, Cai Y, Matthaei K, Foster P. Comparative roles of IL-4, IL-13, and IL-4Ralpha in dendritic cell maturation and CD4+ Th2 cell function. J Immunol. 2007;178:219-27 pubmed
    ..The affinity of IL-4Ralpha also appears to be a determinant in the balance between Th2 and IFN-gamma responses and thus the severity of allergic disease. ..
  33. Mosley B, Beckmann M, March C, Idzerda R, Gimpel S, Vandenbos T, et al. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989;59:335-48 pubmed
    ..The soluble form of the IL-4 receptor blocked the ability of IL-4 to induce CTLL cell proliferation and may represent a regulatory molecule specific for IL-4-dependent immune responses. ..
  34. DeNardo D, Barreto J, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16:91-102 pubmed publisher
  35. Wermeling F, Anthony R, Brombacher F, Ravetch J. Acute inflammation primes myeloid effector cells for anti-inflammatory STAT6 signaling. Proc Natl Acad Sci U S A. 2013;110:13487-91 pubmed publisher
    ..this cytokine on myeloid effector cells, depending on their expression of the IL-4 receptor alpha chain (IL-4Rα/CD124)...
  36. Qiu Y, Nguyen K, Odegaard J, Cui X, Tian X, Locksley R, et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell. 2014;157:1292-308 pubmed publisher
    ..Together, our findings have uncovered the efferent circuit controlling biogenesis of beige fat and provide support for its targeting to treat obesity. ..
  37. Nieuwenhuizen N, Kirstein F, Jayakumar J, Emedi B, Hurdayal R, Horsnell W, et al. Allergic airway disease is unaffected by the absence of IL-4R?-dependent alternatively activated macrophages. J Allergy Clin Immunol. 2012;130:743-750.e8 pubmed publisher
  38. Herbert D, Yang J, Hogan S, Groschwitz K, Khodoun M, Munitz A, et al. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med. 2009;206:2947-57 pubmed publisher
  39. Schnyder Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, et al. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med. 2006;203:2715-25 pubmed
    ..Although it is essential during antigen sensitization to establish allergic asthma, in sensitized mice IL-17 attenuates the allergic response by inhibiting DCs and chemokine synthesis. ..
  40. Kurowska Stolarska M, Stolarski B, Kewin P, Murphy G, Corrigan C, Ying S, et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol. 2009;183:6469-77 pubmed publisher
    ..Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation. ..
  41. Cooney L, Towery K, Endres J, Fox D. Sensitivity and resistance to regulation by IL-4 during Th17 maturation. J Immunol. 2011;187:4440-50 pubmed publisher
    ..Thus, although IL-4 is a potent suppressor of the Th17 genetic program at early stages after differentiation, prolonged stimulation renders Th17 cells impervious to regulatory cytokines. ..
  42. Linde N, Lederle W, Depner S, Van Rooijen N, Gutschalk C, Mueller M. Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J Pathol. 2012;227:17-28 pubmed publisher
    ..However, VEGF-A alone is not sufficient to create a tumour-promoting microenvironment and requires the presence of IL-4 and IL-10 to induce M2 polarization of macrophages. ..
  43. Muller U, Stenzel W, Piehler D, Grahnert A, Protschka M, Kohler G, et al. Abrogation of IL-4 receptor-?-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response. Int Immunol. 2013;25:459-70 pubmed publisher
    ..This is even evident on a relatively resistant heterozygous IL-4R?(+/-) background indicating a key contribution of macrophage IL-4R? expression to susceptibility in allergic bronchopulmonary mycosis. ..
  44. Nguyen K, Qiu Y, Cui X, Goh Y, Mwangi J, David T, et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011;480:104-8 pubmed publisher
    ..Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold. ..
  45. Hilton D, Zhang J, Metcalf D, Alexander W, Nicola N, Willson T. Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sci U S A. 1996;93:497-501 pubmed
    ..These results suggest that the IL-13 receptor alpha chain (NR4) is the primary binding subunit of the IL-13 receptor and may also be a component of IL-4 receptors. ..
  46. Stager S, Alexander J, Carter K, Brombacher F, Kaye P. Both interleukin-4 (IL-4) and IL-4 receptor alpha signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity. Infect Immun. 2003;71:4804-7 pubmed
    ..IL-4 and IL-13 appear to play little role in regulating collagen deposition in L. donovani-induced granulomas. ..
  47. Gavett S, O Hearn D, Karp C, Patel E, Schofield B, Finkelman F, et al. Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice. Am J Physiol. 1997;272:L253-61 pubmed
    ..These results demonstrate that IL-4 is necessary for in vivo development of antigen-induced AHR, goblet cell metaplasia, and pulmonary eosinophilia...
  48. Balic A, Harcus Y, Taylor M, Brombacher F, Maizels R. IL-4R signaling is required to induce IL-10 for the establishment of T(h)2 dominance. Int Immunol. 2006;18:1421-31 pubmed
    ..We conclude that T(h)2 cell development in response to N. brasiliensis antigen requires both IL-4 and IL-10 to act in concert on incipient populations of both T(h)1 and T(h)2 types. ..
  49. Horsnell W, Cutler A, Hoving J, Hoving C, Mearns H, Myburgh E, et al. Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice. PLoS Pathog. 2007;3:e1 pubmed
    ..brasiliensis expulsion by coordinating T helper 2 cytokine responses, goblet hyperplasia, and acetylcholine responsiveness, which drive smooth muscle cell contractions. ..
  50. Wrighton N, Campbell L, Harada N, Miyajima A, Lee F. The murine interleukin-4 receptor gene: genomic structure, expression and potential for alternative splicing. Growth Factors. 1992;6:103-18 pubmed
    ..Such homology at the levels of both protein and gene structure suggest a divergent evolution of the receptors from a single primordial gene. ..
  51. Kelly Welch A, Melo M, Smith E, Ford A, Haudenschild C, Noben Trauth N, et al. Complex role of the IL-4 receptor alpha in a murine model of airway inflammation: expression of the IL-4 receptor alpha on nonlymphoid cells of bone marrow origin contributes to severity of inflammation. J Immunol. 2004;172:4545-55 pubmed
    ..These results suggest that IL-4 and IL-13 contribute to the development of allergic inflammation by stimulating a complex interaction between IL-4Ralpha(+) cell types of both bone marrow and non-bone marrow origin. ..
  52. Urban J, Noben Trauth N, Schopf L, Madden K, Finkelman F. Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites. J Immunol. 2001;167:6078-81 pubmed
    ..Thus, direct IL-4Ralpha signaling of nonimmune gastrointestinal cells may be generally required to induce worm expulsion, even when mast cell and T cell responses are also required...
  53. Wojciechowski W, Harris D, Sprague F, Mousseau B, Makris M, Kusser K, et al. Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity. 2009;30:421-33 pubmed publisher
    ..These results show that B cells mediate protection from pathogens not only by presenting antigen and secreting antibody but also by producing cytokines that regulate the quality and magnitude of humoral and cellular immune responses...
  54. Padilla J, Daley E, Chow A, Robinson K, Parthasarathi K, McKenzie A, et al. IL-13 regulates the immune response to inhaled antigens. J Immunol. 2005;174:8097-105 pubmed
    ..These data indicate that blockade of IL-13 may have therapeutic potential for controlling the immune response to inhaled Ags. ..
  55. Harada N, Castle B, Gorman D, Itoh N, Schreurs J, Barrett R, et al. Expression cloning of a cDNA encoding the murine interleukin 4 receptor based on ligand binding. Proc Natl Acad Sci U S A. 1990;87:857-61 pubmed
  56. Hasnain S, Evans C, Roy M, Gallagher A, Kindrachuk K, Barron L, et al. Muc5ac: a critical component mediating the rejection of enteric nematodes. J Exp Med. 2011;208:893-900 pubmed publisher
    ..Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection...
  57. Blaeser F, Bryce P, Ho N, Raman V, Dedeoglu F, Donaldson D, et al. Targeted inactivation of the IL-4 receptor alpha chain I4R motif promotes allergic airway inflammation. J Exp Med. 2003;198:1189-200 pubmed
    ..These results define an important role for the I4R motif in regulating allergic inflammation. ..
  58. Muller U, Stenzel W, Kohler G, Polte T, Blessing M, Mann A, et al. A gene-dosage effect for interleukin-4 receptor alpha-chain expression has an impact on Th2-mediated allergic inflammation during bronchopulmonary mycosis. J Infect Dis. 2008;198:1714-21 pubmed publisher
    ..mice and no expression in IL-4Ralpha(-/-) mice, indicating biallelic expression of the gene for IL-4Ralpha (Il4ra)...
  59. Rückerl D, Jenkins S, Laqtom N, Gallagher I, Sutherland T, Duncan S, et al. Induction of IL-4Rα-dependent microRNAs identifies PI3K/Akt signaling as essential for IL-4-driven murine macrophage proliferation in vivo. Blood. 2012;120:2307-16 pubmed publisher
    ..Together, the data suggest that negative regulation of Akt signaling via microRNAs might play a central role in limiting MΦ expansion and alternative activation during type 2 inflammatory settings. ..
  60. Kuperman D, Huang X, Nguyenvu L, Holscher C, Brombacher F, Erle D. IL-4 receptor signaling in Clara cells is required for allergen-induced mucus production. J Immunol. 2005;175:3746-52 pubmed
    ..Because only IL-13 and IL-4 are thought to signal via IL-4Ralpha, we conclude that direct effects of IL-4 and/or IL-13 on Clara cells are required for allergen-induced mucus production in the airway epithelium. ..
  61. Tachdjian R, Mathias C, Al Khatib S, Bryce P, Kim H, Blaeser F, et al. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med. 2009;206:2191-204 pubmed publisher
    ..Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4R alpha-dependent signaling. ..
  62. Vang K, Yang J, Mahmud S, Burchill M, Vegoe A, Farrar M. IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J Immunol. 2008;181:3285-90 pubmed
  63. Kirstein F, Horsnell W, Kuperman D, Huang X, Erle D, Lopata A, et al. Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma. J Allergy Clin Immunol. 2010;126:347-54 pubmed publisher
    ..These findings suggest that IL-4Ralpha responsiveness in airway smooth muscle cells during the early phase of allergic asthma is not, as suggested, necessary for the outcome of the disease. ..
  64. Herbert D, Orekov T, Roloson A, Ilies M, Perkins C, O BRIEN W, et al. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J Immunol. 2010;184:6438-46 pubmed publisher
    ..Thus, macrophage-derived Arg I protects hosts against excessive tissue injury caused by worm eggs during acute schistosomiasis by suppressing IL-12/IL-23p40 production and maintaining the Treg/Th17 balance within the intestinal mucosa. ..
  65. Strait R, Morris S, Smiley K, Urban J, Finkelman F. IL-4 exacerbates anaphylaxis. J Immunol. 2003;170:3835-42 pubmed
    ..Synergy between IL-4 and vasoactive mediators during the effector phase of allergic inflammation may both contribute to allergic immunopathology and enhance protective immunity against gastrointestinal worms. ..
  66. Ueda N, Kuki H, Kamimura D, Sawa S, Seino K, Tashiro T, et al. CD1d-restricted NKT cell activation enhanced homeostatic proliferation of CD8+ T cells in a manner dependent on IL-4. Int Immunol. 2006;18:1397-404 pubmed
    ..Thus, these results showed the 'involvement' of IL-4 that is produced from activated NKT cells for CD8+ T cell homeostatic proliferation in vivo. ..
  67. Maldonado R, Soriano M, Perdomo L, Sigrist K, Irvine D, Decker T, et al. Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse. J Exp Med. 2009;206:877-92 pubmed publisher
    ..Th1 effector cells, an event regulated by signaling through the functionally opposing receptor to interleukin-4 (IL4R)...
  68. Webb D, Matthaei K, Cai Y, McKenzie A, Foster P. Polymorphisms in IL-4R alpha correlate with airways hyperreactivity, eosinophilia, and Ym protein expression in allergic IL-13-/- mice. J Immunol. 2004;172:1092-8 pubmed
    ..Collectively, these data show that polymorphisms in IL-4Ralpha, which have been shown to affect the interaction with IL-4, correlate with the ability of IL-4 to regulate allergic responses in IL-13(-/-) mice. ..
  69. Marillier R, Brombacher T, Dewals B, Leeto M, Barkhuizen M, Govender D, et al. IL-4R{alpha}-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis. Am J Physiol Gastrointest Liver Physiol. 2010;298:G943-51 pubmed publisher
    ..mansoni eggs and to prevent premature mortality...
  70. Koller F, Hwang D, Dozier E, Fingleton B. Epithelial interleukin-4 receptor expression promotes colon tumor growth. Carcinogenesis. 2010;31:1010-7 pubmed publisher
    ..An orthotopic allograft model was used to determine in vivo effects of tumor cell-specific IL4Ra ablation...
  71. Mohrs M, Ledermann B, Kohler G, Dorfmüller A, Gessner A, Brombacher F. Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J Immunol. 1999;162:7302-8 pubmed
    ..major, mediated by a functional IL-13 receptor. ..
  72. Noben Trauth N, Paul W, Sacks D. IL-4- and IL-4 receptor-deficient BALB/c mice reveal differences in susceptibility to Leishmania major parasite substrains. J Immunol. 1999;162:6132-40 pubmed
    ..major infection. The results with LV39 infection indicate that yet another unidentified factor is capable of causing susceptibility to L. major in the absence of IL-4 or IL-4 signaling. ..