Il6ra

Summary

Gene Symbol: Il6ra
Description: interleukin 6 receptor, alpha
Alias: CD126, IL-6R, IL-6R-alpha, IL-6RA, Il6r, interleukin-6 receptor subunit alpha, IL-6 receptor alpha chain, IL-6 receptor subunit alpha, IL-6R 1, IL-6R subunit alpha
Species: mouse
Products:     Il6ra

Top Publications

  1. Sugita T, Totsuka T, Saito M, Yamasaki K, Taga T, Hirano T, et al. Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis. J Exp Med. 1990;171:2001-9 pubmed
    ..Since IL-6 functions as a potent growth factor for murine plasmacytomas, over-expression of abnormal IL-6-R may function as a positive selection element for the development of certain plasmacytomas. ..
  2. Okazaki M, Yamada Y, Nishimoto N, Yoshizaki K, Mihara M. Characterization of anti-mouse interleukin-6 receptor antibody. Immunol Lett. 2002;84:231-40 pubmed
    ..These lines of evidence demonstrate that MR16-1 is useful to investigate the physiological and pathological roles of IL-6 and sIL-6R in mice. ..
  3. McClanahan T, Dalrymple S, Barkett M, Lee F. Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells. Blood. 1993;81:2903-15 pubmed
    ..The defined temporal order for the expression of these genes suggests that they may be useful as markers for multiple stages in the development of different hematopoietic cell lineages during embryogenesis. ..
  4. Peters M, Schirmacher P, Goldschmitt J, Odenthal M, Peschel C, Fattori E, et al. Extramedullary expansion of hematopoietic progenitor cells in interleukin (IL)-6-sIL-6R double transgenic mice. J Exp Med. 1997;185:755-66 pubmed
    ..gp130 activators may become important for the expansion of hematopoietic progenitor cells in vivo and in vitro. ..
  5. Wunderlich C, Delic D, Behnke K, Meryk A, Ströhle P, Chaurasia B, et al. Cutting edge: Inhibition of IL-6 trans-signaling protects from malaria-induced lethality in mice. J Immunol. 2012;188:4141-4 pubmed publisher
    ..Therefore, inhibition of IL-6 trans-signaling may serve as a novel promising therapeutic basis to combat malaria. ..
  6. Castellino F, Germain R. Chemokine-guided CD4+ T cell help enhances generation of IL-6RalphahighIL-7Ralpha high prememory CD8+ T cells. J Immunol. 2007;178:778-87 pubmed
    ..They also reveal that elevated IL-6Ralpha expression by a subset of CD8(+) T cells represents an early imprint of CD4(+) T cell helper function that actively contributes to the survival of activated CD8(+) T cells. ..
  7. Crabé S, Guay Giroux A, Tormo A, Duluc D, Lissilaa R, Guilhot F, et al. The IL-27 p28 subunit binds cytokine-like factor 1 to form a cytokine regulating NK and T cell activities requiring IL-6R for signaling. J Immunol. 2009;183:7692-702 pubmed publisher
    ..The identification of a new IL-6R ligand is therefore important for a complete understanding of the mechanism of action of this emerging class of immunosuppressors. ..
  8. Chalaris A, Gewiese J, Paliga K, Fleig L, Schneede A, Krieger K, et al. ADAM17-mediated shedding of the IL6R induces cleavage of the membrane stub by gamma-secretase. Biochim Biophys Acta. 2010;1803:234-45 pubmed publisher
    ..In classic signaling, IL6 first binds to the membrane bound Interleukin-6 Receptor (IL6R) whereas in trans-signaling, IL6 acts via a soluble form of the IL6R...
  9. Jones G, McLoughlin R, Hammond V, Parker C, Williams J, Malhotra R, et al. Loss of CD4+ T cell IL-6R expression during inflammation underlines a role for IL-6 trans signaling in the local maintenance of Th17 cells. J Immunol. 2010;184:2130-9 pubmed publisher
    IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) alpha subunit (classical IL-6R signaling) or through a soluble form of this cognate receptor (IL-6 trans signaling)...

More Information

Publications84

  1. Garbers C, Spudy B, Aparicio Siegmund S, Waetzig G, Sommer J, Holscher C, et al. An interleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer. J Biol Chem. 2013;288:4346-54 pubmed publisher
    ..The binding of p28 to a gp130/Wsx-1 heterodimer or a gp130 homodimer is highly selective and controlled by a novel molecular switch induced by EBI3 or IL-6R, respectively. ..
  2. Jia G, Gutierrez Ramos J. Analysis of interleukin receptor gene expression in mouse fetal liver by quantitative polymerase chain reaction. Eur J Immunol. 1995;25:2096-100 pubmed
    ..Their expression seems to precede that of the genes encoding the specific subunits of these interleukin receptor systems. ..
  3. Matsumoto S, Hara T, Mitsuyama K, Yamamoto M, Tsuruta O, Sata M, et al. Essential roles of IL-6 trans-signaling in colonic epithelial cells, induced by the IL-6/soluble-IL-6 receptor derived from lamina propria macrophages, on the development of colitis-associated premalignant cancer in a murine model. J Immunol. 2010;184:1543-51 pubmed publisher
    ..Treatment with soluble gp130Fc significantly reduced the CApC. IL-6 trans-signaling in epithelial cells induced by macrophage-derived IL-6/sIL-6R alpha plays a crucial role in the development of CAC. ..
  4. Wunderlich F, Ströhle P, Könner A, Gruber S, Tovar S, Brönneke H, et al. Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. Cell Metab. 2010;12:237-49 pubmed publisher
    ..Thus, our results reveal an unexpected role for hepatic IL-6 signaling to limit hepatic inflammation and to protect from local and systemic insulin resistance. ..
  5. McFarland Mancini M, Funk H, Paluch A, Zhou M, Giridhar P, Mercer C, et al. Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor. J Immunol. 2010;184:7219-28 pubmed publisher
    ..These findings underscore a deeper complexity for IL-6Ralpha function in inflammation than has been recognized previously. ..
  6. de Souza C, Morel L, Cabrera W, Starobinas N, Ribeiro O, Siqueira M, et al. Quantitative trait loci in Chromosomes 3, 8, and 9 regulate antibody production against Salmonella flagellar antigens in the mouse. Mamm Genome. 2004;15:630-6 pubmed
    ..HIII and LIII lines differ in the resistance to several diseases, therefore, the relevance of these QTL with the genetic factors involved in infections, autoimmunity, and neoplastic disease progression is discussed. ..
  7. de Silva K, Daud A, Deng J, Jones S, Gamelli R, Shankar R. Prostaglandin E2 mediates growth arrest in NFS-60 cells by down-regulating interleukin-6 receptor expression. Biochem J. 2003;370:315-21 pubmed
    ..The present study demonstrates that PGE2 is a potent down-regulator of IL-6r expression and thus may provide a mechanistic explanation for the granulocytopenia seen in thermal injury and sepsis. ..
  8. Melnick M, Chen H, Zhou Y, Jaskoll T. Interleukin-6 signaling and embryonic mouse submandibular salivary gland morphogenesis. Cells Tissues Organs. 2001;168:233-45 pubmed
    ..Taken together, our experimental results indicate that IL-6 signaling is important to SMG developmental homeostasis. ..
  9. Saito T, Yasukawa K, Suzuki H, Futatsugi K, Fukunaga T, Yokomizo C, et al. Preparation of soluble murine IL-6 receptor and anti-murine IL-6 receptor antibodies. J Immunol. 1991;147:168-73 pubmed
    ..One of the clones, RS13, produced IgG2a isotype that was capable of inhibiting IL-6 activity. ELISA for the quantitation of smIL-6R was established, which could detect smIL-6R in a quantity as low as 1 ng/ml. ..
  10. Chalaris A, Rabe B, Paliga K, Lange H, Laskay T, Fielding C, et al. Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils. Blood. 2007;110:1748-55 pubmed
    ..Apoptosis-induced shedding of the IL6R was caspase dependent but PKC independent, with inhibition of ADAM17 preventing IL6R shedding...
  11. Heath V, Suh H, Holman M, Renn K, Gooya J, Parkin S, et al. C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood. 2004;104:1639-47 pubmed
    ..These findings show that C/EBPalpha deficiency results in hyperproliferation of HPCs and a block in the ability of multipotential progenitors to differentiate into bipotential granulocyte/macrophage progenitors and their progeny. ..
  12. Gerwin N, Jia G, Kulbacki R, Gutierrez Ramos J. Interleukin gene expression in mouse preimplantation development. Dev Immunol. 1995;4:169-79 pubmed
    ..The controlled expression of these "inflammatory-type" cytokines and their receptors suggests a role for these growth factors during the early phases of mouse ontogeny. ..
  13. Schéle E, Fekete C, Egri P, Fuzesi T, Palkovits M, Keller E, et al. Interleukin-6 receptor ? is co-localised with melanin-concentrating hormone in human and mouse hypothalamus. J Neuroendocrinol. 2012;24:930-43 pubmed publisher
    ..This opens up the possibility that IL-6 influences the energy balance through the MCH neurones in humans, and both MCH and orexin neurones in mice. ..
  14. Hartman M, Vreeswijk Baudoin I, Groot H, van de Kolk K, de Boer R, Mateo Leach I, et al. Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion. PLoS ONE. 2016;11:e0167195 pubmed publisher
  15. Massoud A, Charbonnier L, Lopez D, Pellegrini M, Phipatanakul W, Chatila T. An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells. Nat Med. 2016;22:1013-22 pubmed publisher
    ..Treg cell-specific deletion of genes that regulate TH17 cell differentiation, including Il6ra and RAR-related orphan receptor gamma (Rorc), but not of Il4 or Il13, prevented exacerbated airway inflammation in ..
  16. Theurich S, Tsaousidou E, Hanssen R, Lempradl A, Mauer J, Timper K, et al. IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metab. 2017;26:171-184.e6 pubmed publisher
    ..Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of these myeloid signature NK cells, protecting from ..
  17. Wang X, Schunck M, Kallen K, Neumann C, Trautwein C, Rose John S, et al. The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. J Invest Dermatol. 2004;123:124-31 pubmed
    ..Our results indicate that the IL-6 cytokine system, particularly transsignalling via the soluble IL-6R, is critically involved in barrier repair after skin injury. ..
  18. Rosser E, Oleinika K, Tonon S, Doyle R, Bosma A, Carter N, et al. Regulatory B cells are induced by gut microbiota-driven interleukin-1β and interleukin-6 production. Nat Med. 2014;20:1334-9 pubmed publisher
    ..Thus, in response to inflammatory signals induced by both the gut flora and arthritis, Breg cells increase in number and restrain excessive inflammation. ..
  19. Zhang P, Iwama A, Datta M, Darlington G, Link D, Tenen D. Upregulation of interleukin 6 and granulocyte colony-stimulating factor receptors by transcription factor CCAAT enhancer binding protein alpha (C/EBP alpha) is critical for granulopoiesis. J Exp Med. 1998;188:1173-84 pubmed
    ..The results of these and other studies suggest that additional C/EBPalpha target genes, possibly other cytokine receptors, are also important for the block in granulocyte differentiation observed in vivo in C/EBPalpha-deficient mice. ..
  20. Tsukasaki M, Komatsu N, Nagashima K, Nitta T, Pluemsakunthai W, Shukunami C, et al. Host defense against oral microbiota by bone-damaging T cells. Nat Commun. 2018;9:701 pubmed publisher
    ..Thus, bone-damaging T cells, which may have developed to stop local infection by inducing tooth loss, function as a double-edged sword by protecting against pathogens while also inducing skeletal tissue degradation. ..
  21. Fiorillo M, Toniatti C, Van Snick J, Ciliberto G. Expression of the murine interleukin 6 receptor in hepatoma cells: the intracytoplasmic domain is not required for interleukin 6 signal transduction. Eur J Immunol. 1992;22:799-804 pubmed
    ..e. CRP promoter activation), but that the last 40 amino acids contribute to maximal IL6 response in these cells. ..
  22. Fielding C, Jones G, McLoughlin R, McLeod L, Hammond V, Uceda J, et al. Interleukin-6 signaling drives fibrosis in unresolved inflammation. Immunity. 2014;40:40-50 pubmed publisher
    ..Thus, IL-6 causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation. ..
  23. Nish S, Schenten D, Wunderlich F, Pope S, Gao Y, Hoshi N, et al. T cell-intrinsic role of IL-6 signaling in primary and memory responses. elife. 2014;3:e01949 pubmed publisher
    ..DOI: http://dx.doi.org/10.7554/eLife.01949.001. ..
  24. Brunello A, Weissenberger J, Kappeler A, Vallan C, Peters M, Rose John S, et al. Astrocytic alterations in interleukin-6/Soluble interleukin-6 receptor alpha double-transgenic mice. Am J Pathol. 2000;157:1485-93 pubmed
    ..The BBB remains primarily intact. IL-6/IL-6Ralpha, however, might be directly responsible for the selective activation of astrocytes. ..
  25. Li Y, Bäckesjö C, Haldosén L, Lindgren U. IL-6 receptor expression and IL-6 effects change during osteoblast differentiation. Cytokine. 2008;43:165-73 pubmed publisher
    ..The present study shows that IL-6 receptor expression increases during in vitro osteoblast differentiation and that IL-6 functions as a differentiation regulator of preosteoblast cells and an apoptosis initiator in more mature cells. ..
  26. Mahadevan N, Rodvold J, Sepulveda H, Rossi S, Drew A, Zanetti M. Transmission of endoplasmic reticulum stress and pro-inflammation from tumor cells to myeloid cells. Proc Natl Acad Sci U S A. 2011;108:6561-6 pubmed publisher
    ..Although neither Toll-like receptor (TLR)2 nor interleukin 6 receptor (IL6R) signaling is involved, a reduction was observed in the transmission of ER stress to TLR4 KO macrophages, ..
  27. Atsumi T, Ishihara K, Kamimura D, Ikushima H, Ohtani T, Hirota S, et al. A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis. J Exp Med. 2002;196:979-90 pubmed
    ..Finally, we showed that disease development was dependent on lymphocytes. These results provide evidence that a point mutation of a cytokine receptor has the potential to induce autoimmune disease. ..
  28. Baran P, Nitz R, Grötzinger J, Scheller J, Garbers C. Minimal interleukin 6 (IL-6) receptor stalk composition for IL-6 receptor shedding and IL-6 classic signaling. J Biol Chem. 2013;288:14756-68 pubmed publisher
    ..In IL-6 trans-signaling, it regulates proper proteolysis by ADAM10 and ADAM17. In IL-6 classic-signaling, it acts as a spacer to ensure IL-6·IL-6R·gp130 signal complex formation. ..
  29. Slutsky S, Kamaraju A, Levy A, Chebath J, Revel M. Activation of myelin genes during transdifferentiation from melanoma to glial cell phenotype. J Biol Chem. 2003;278:8960-8 pubmed
  30. Suzuki H, Yasukawa K, Saito T, Narazaki M, Hasegawa A, Taga T, et al. Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. Eur J Immunol. 1993;23:1078-82 pubmed
  31. Ren F, Geng Y, Minami T, Qiu Y, Feng Y, Liu C, et al. Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP. FEBS Lett. 2015;589:1890-6 pubmed publisher
    ..These results suggest that SIPAR terminates the activation of STAT3 through a dephosphorylation process that is dependent upon interaction with TC45 in the nucleus. ..
  32. Iida S, Omoto K, Kanemitsu I, Setoguchi K, Ishida H, Tanabe K, et al. Interleukin-6 receptor signaling disruption prevents cardiac allograft deterioration in mice. Exp Clin Transplant. 2012;10:375-85 pubmed publisher
    ..Disruption of interleukin-6 receptor signaling is an effective strategy for modulating proinflammatory immune responses and preventing chronic rejection. ..
  33. Schirmacher P, Peters M, Ciliberto G, Blessing M, Lotz J, Meyer zum Buschenfelde K, et al. Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. Am J Pathol. 1998;153:639-48 pubmed
  34. Balabko L, Andreev K, Burmann N, Schubert M, Mathews M, Trufa D, et al. Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung. Sci Rep. 2014;4:7396 pubmed publisher
    Here we describe increased expression of IL6R in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to squamous cell lung carcinoma...
  35. Li B, Gurung P, Malireddi R, Vogel P, Kanneganti T, Geiger T. IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis. Nat Commun. 2015;6:6131 pubmed publisher
    ..Therefore, lineage-specific effects of IL-10 skew the cytokine dependency of Th17 cell development required for colitis pathogenesis. Coordinated interventions may be needed to fully suppress Th17-mediated immunopathology. ..
  36. Gomez M, Sokol S, Muir A, Soong G, Bastien J, Prince A. Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling. J Immunol. 2005;175:1930-6 pubmed
    ..Thus, bacteria are physiological activators of TACE expression, which provides a mechanism to regulate inflammatory signaling that is initiated by airway epithelial cells. ..
  37. Einbond A, Sudol M. Towards prediction of cognate complexes between the WW domain and proline-rich ligands. FEBS Lett. 1996;384:1-8 pubmed
    ..Should these predictions be proven empirically, the results may have important ramifications for basic research and medicine. ..
  38. Cosman D. The hematopoietin receptor superfamily. Cytokine. 1993;5:95-106 pubmed
  39. Zhang C, Xin H, Zhang W, Yazaki P, Zhang Z, Le K, et al. CD5 Binds to Interleukin-6 and Induces a Feed-Forward Loop with the Transcription Factor STAT3 in B Cells to Promote Cancer. Immunity. 2016;44:913-923 pubmed publisher
    ..CD5(+) B cells also showed activation of STAT3 in multiple types of human tumor tissues. Thus, our findings demonstrate a critical role of CD5(+) B cells in promoting cancer. ..
  40. Anesten F, Holt M, Schéle E, Pálsdóttir V, Reimann F, Gribble F, et al. Preproglucagon neurons in the hindbrain have IL-6 receptor-α and show Ca2+ influx in response to IL-6. Am J Physiol Regul Integr Comp Physiol. 2016;311:R115-23 pubmed publisher
    ..In summary, IL-6Rα is present on PPG neurons in the NTS, and IL-6 can stimulate these cells by increasing influx of Ca(2+) to the cytosol from the extracellular space. ..
  41. Oh K, Lee O, Shon S, Nam O, Ryu P, Seo M, et al. A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res. 2013;15:R79 pubmed
    ..This potential tumor-MDSC axis involving IL-6 trans-signaling directly affected breast cancer cell aggressiveness, leading to spontaneous metastasis. ..
  42. Ikeda K, Kinoshita M, Tagaya N, Shiojima T, Taga T, Yasukawa K, et al. Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease. Brain Res. 1996;726:91-7 pubmed
    ..We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130. ..
  43. Wang S, Reinhard S, Li C, Qian M, Jiang H, Du Y, et al. Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to Glioma. Mol Ther. 2017;25:1556-1566 pubmed publisher
    ..The results denote that I6P7 peptide is a roborant cascade-targeting ligand, and I6P7-modified NPs might be exploited for efficient glioma therapy. ..
  44. Mathews C, Dunn B, Hannigan M, Huang C, Leiter E. Genetic control of neutrophil superoxide production in diabetes-resistant ALR/Lt mice. Free Radic Biol Med. 2002;32:744-51 pubmed
  45. Ma X, Reynolds S, Baker B, Li X, Benveniste E, Qin H. IL-17 enhancement of the IL-6 signaling cascade in astrocytes. J Immunol. 2010;184:4898-906 pubmed publisher
    ..These results indicate that astrocytes can serve as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 functions in the CNS as a negative feedback regulator. ..
  46. Jensen J, Peters L, Borrego A, Ribeiro O, Cabrera W, Starobinas N, et al. Involvement of antibody production quantitative trait loci in the susceptibility to pristane-induced arthritis in the mouse. Genes Immun. 2006;7:44-50 pubmed
    ..Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes. ..
  47. Lin W, Yi Z, Stunz L, Maine C, Sherman L, Bishop G. The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development. Sci Signal. 2015;8:ra88 pubmed publisher
    ..Our findings identify TRAF3 and PTPN22 as inhibitors of IL-6R signaling in B cells and reveal a previously uncharacterized role for TRAF3 in the regulation of plasma cell differentiation. ..
  48. Yoder M, Hiatt K, Dutt P, Mukherjee P, Bodine D, Orlic D. Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. Immunity. 1997;7:335-44 pubmed
    ..Surprisingly, 37-fold more CD34+c-Kit+ cells reside in the day 9 yolk sac than in the P-Sp. In sum, definitive HSC are coexistent, but not equal in number, in the murine yolk sac and P-Sp prior to fetal liver colonization. ..
  49. Sommer J, Engelowski E, Baran P, Garbers C, Floss D, Scheller J. Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis. Int J Mol Med. 2014;34:651-60 pubmed publisher
    ..Our data suggest that IL-6 and IL-6R have an additional role in colitis, apart from the IL-6/IL-6R classic and trans-signaling. ..
  50. Pham D, Walline C, Hollister K, Dent A, Blum J, Firulli A, et al. The transcription factor Twist1 limits T helper 17 and T follicular helper cell development by repressing the gene encoding the interleukin-6 receptor ? chain. J Biol Chem. 2013;288:27423-33 pubmed publisher
    ..factor Twist1 as a component of a STAT3-induced feedback loop that controls IL-6 signals by directly repressing Il6ra. Human and mouse T cells lacking Twist1 have an increased ability to differentiate into Th17 cells...
  51. Ueda O, Tateishi H, Higuchi Y, Fujii E, Kato A, Kawase Y, et al. Novel genetically-humanized mouse model established to evaluate efficacy of therapeutic agents to human interleukin-6 receptor. Sci Rep. 2013;3:1196 pubmed publisher
    ..disease mouse model, in which the endogenous interleukin-6 receptor gene is successfully replaced by human IL6R, and human IL6 is overexpressed...
  52. Quintana A, Erta M, Ferrer B, Comes G, Giralt M, Hidalgo J. Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior. Brain Behav Immun. 2013;27:162-73 pubmed publisher
    ..KO mice), and have compared their phenotype with that of mice with deletion of IL-6 receptor in astrocytes (Ast-IL6R KO mice)...
  53. Harker J, Lewis G, Mack L, Zuniga E. Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection. Science. 2011;334:825-9 pubmed publisher
    ..This resulted in escalation of germinal center reactions and improved antibody responses. Our results uncover an antiviral strategy that helps to safely resolve a persistent infection in vivo...
  54. Jeong S, Kim J, Lee C, Park Y, Kim S, Yoon S, et al. Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals. Immunobiology. 2017;222:55-65 pubmed publisher
    ..Thus, we present evidence for the role of M2 phenotype TAM in IL-6 receptor-mediated signals, particularly tyrosine phosphorylation of STAT3, responsible for the prosurvival adaptation of tumor cells to hypoxia. ..
  55. Kiuchi N, Nakajima K, Ichiba M, Fukada T, Narimatsu M, Mizuno K, et al. STAT3 is required for the gp130-mediated full activation of the c-myc gene. J Exp Med. 1999;189:63-73 pubmed
    ..This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene. ..
  56. Jaskoll T, Melnick M. Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations. Anat Rec. 1999;256:252-68 pubmed
    ..These and other findings provide insight into the design of future functional studies. ..
  57. Axmann R, Böhm C, Kronke G, Zwerina J, Smolen J, Schett G. Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum. 2009;60:2747-56 pubmed publisher
    ..This effect adds significantly to the structure-sparing potential of pharmacologic blockade of IL-6R in arthritis. ..
  58. Gewiese Rabsch J, Drucker C, Malchow S, Scheller J, Rose John S. Role of IL-6 trans-signaling in CCl?induced liver damage. Biochim Biophys Acta. 2010;1802:1054-61 pubmed publisher
    ..We conclude that IL-6 trans-signaling via the soluble IL-6R is important for the physiologic response of the liver to CCl? induced chemical damage. ..
  59. Sharma M, Shinde R, McGaha T, Huang L, Holmgaard R, Wolchok J, et al. The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment. Sci Adv. 2015;1:e1500845 pubmed publisher
    ..Thus, the immunosuppressive milieu in tumors must be actively maintained, and tumors become susceptible to immune attack if the PTEN pathway in Tregs is disrupted. ..
  60. Tsukamoto H, Fujieda K, Hirayama M, Ikeda T, Yuno A, Matsumura K, et al. Soluble IL6R Expressed by Myeloid Cells Reduces Tumor-Specific Th1 Differentiation and Drives Tumor Progression. Cancer Res. 2017;77:2279-2291 pubmed publisher
    ..increase of sIL6R was not prominent in tumor-bearing mice with myeloid cell-specific conditional deletion of IL6R even when tumor cells produced sIL6R...
  61. Garbers C, Thaiss W, Jones G, Waetzig G, Lorenzen I, Guilhot F, et al. Inhibition of classic signaling is a novel function of soluble glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J Biol Chem. 2011;286:42959-70 pubmed publisher
  62. Suzuki M, Yoshida H, Hashizume M, Tanaka K, Matsumoto Y. Blockade of interleukin-6 receptor enhances the anti-arthritic effect of glucocorticoids without decreasing bone mineral density in mice with collagen-induced arthritis. Clin Exp Immunol. 2015;182:154-61 pubmed publisher
    ..We demonstrated that IL-6 signalling blockade by an anti-IL-6R antibody can augment the anti-arthritic effect of GCs and inhibit the bone loss they cause. ..
  63. Badalova J, Svobodova M, Havelková H, Vladimirov V, Vojtísková J, Engová J, et al. Separation and mapping of multiple genes that control IgE level in Leishmania major infected mice. Genes Immun. 2002;3:187-95 pubmed
    ..The definition of genes controlling anti-parasite responses will permit a better understanding of pathways and genetic diversity underlying the disease phenotypes. ..
  64. Eskilsson A, Mirrasekhian E, Dufour S, Schwaninger M, Engblom D, Blomqvist A. Immune-induced fever is mediated by IL-6 receptors on brain endothelial cells coupled to STAT3-dependent induction of brain endothelial prostaglandin synthesis. J Neurosci. 2014;34:15957-61 pubmed publisher
  65. Iwasaki T, Hamano T, Fujimoto J, Kakishita E. Regulation of interleukin-6 and interleukin-6R alpha (gp80) expression by murine immunoglobulin-secreting B-cell hybridomas. Immunology. 1998;93:498-504 pubmed
    ..These findings provide a role by which T-cell-dependent activation through CD40 regulates an IL-6 autocrine loop, controlling B-cell differentiation. ..
  66. Zelenay S, Bergman M, Paiva R, Lino A, Martins A, Duarte J, et al. Cutting edge: Intrathymic differentiation of adaptive Foxp3+ regulatory T cells upon peripheral proinflammatory immunization. J Immunol. 2010;185:3829-33 pubmed publisher
    ..Our findings uncover a pathway for T(R) generation with major implications for immunity and tolerance induction...
  67. Gallagher D, Norman A, Woodard C, Yang G, Gauthier Fisher A, Fujitani M, et al. Transient maternal IL-6 mediates long-lasting changes in neural stem cell pools by deregulating an endogenous self-renewal pathway. Cell Stem Cell. 2013;13:564-76 pubmed publisher
  68. Birner P, Heider S, Petzelbauer P, Wolf P, Kornauth C, Kuroll M, et al. Interleukin-6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus. Exp Dermatol. 2016;25:305-10 pubmed publisher
    ..Inhibition of IL-6R signalling might be helpful in lupus cases with predominant skin involvement, but combinatorial treatment might be required to restrain autoantibodies. ..
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