IL 23R

Summary

Gene Symbol: IL 23R
Description: interleukin 23 receptor
Alias: IL-23R, interleukin-23 receptor, IL-23 receptor
Species: mouse
Products:     IL 23R

Top Publications

  1. Petermann F, Rothhammer V, Claussen M, Haas J, Blanco L, Heink S, et al. ?? T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism. Immunity. 2010;33:351-63 pubmed publisher
    ..Thus, IL-23, which by itself has no direct effect on Treg cells, is able to disarm Treg cell responses and promote antigen-specific effector T cell responses via activating ?? T cells. ..
  2. McGeachy M, Chen Y, Tato C, Laurence A, Joyce Shaikh B, Blumenschein W, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10:314-24 pubmed publisher
    ..These defects were associated with less proliferation; consequently, fewer effector T(H)-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues. ..
  3. Chan J, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med. 2006;203:2577-87 pubmed
    ..IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target. ..
  4. Laird R, Laky K, Hayes S. Unexpected role for the B cell-specific Src family kinase B lymphoid kinase in the development of IL-17-producing ?? T cells. J Immunol. 2010;185:6518-27 pubmed publisher
    ..Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. ..
  5. Elyaman W, Bradshaw E, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci U S A. 2009;106:12885-90 pubmed publisher
    ..The mechanism of IL-9 effects on T(H)17 and T(regs) is through activation of STAT3 and STAT5 signaling. Our findings highlight a role of IL-9 as a regulator of pathogenic versus protective mechanisms of immune responses. ..
  6. Riol Blanco L, Lazarevic V, Awasthi A, Mitsdoerffer M, WILSON B, Croxford A, et al. IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. J Immunol. 2010;184:1710-20 pubmed publisher
    ..Our results show that IL-23 regulates the function of IL-17-producing gammadelta and DN T cells, two essential components of the early protective immune response directed against intracellular pathogens. ..
  7. Gocke A, Cravens P, Ben L, Hussain R, Northrop S, Racke M, et al. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J Immunol. 2007;178:1341-8 pubmed
    ..We now show for the first time that suppression of T-bet ameliorates EAE by limiting the differentiation of autoreactive Th1 cells, as well as inhibiting pathogenic Th17 cells via regulation of IL-23R. ..
  8. Awasthi A, Riol Blanco L, Jäger A, Korn T, Pot C, Galileos G, et al. Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells. J Immunol. 2009;182:5904-8 pubmed publisher
  9. Ahern P, Schiering C, Buonocore S, McGeachy M, Cua D, Maloy K, et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity. 2010;33:279-88 pubmed publisher
    ..Together, these results highlight the multiple functions of IL-23 signaling in T cells that contribute to its colitogenic activity. ..

More Information

Publications60

  1. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002;168:5699-708 pubmed
    ..The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2. ..
  2. Cox J, Kljavin N, Ota N, Leonard J, Roose Girma M, Diehl L, et al. Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice. Mucosal Immunol. 2012;5:99-109 pubmed publisher
    ..In summary, we provide evidence for opposing consequences of IL-23R on innate and adaptive lymphoid cells in murine colitis. ..
  3. Rachitskaya A, Hansen A, Horai R, Li Z, Villasmil R, Luger D, et al. Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J Immunol. 2008;180:5167-71 pubmed
    ..These data suggest an important biological role for innate IL-17 production by NKT cells that is rapid and precedes the adaptive IL-17 response. ..
  4. Arbelaez C, Glatigny S, Duhen R, Eberl G, Oukka M, Bettelli E. IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis. J Immunol. 2015;195:1974-83 pubmed publisher
    ..Together, these data address the contribution of IL-23/IL-23R and IL-7/IL-7R signaling in Th17 and Th1 cell dynamics during CNS autoimmunity. ..
  5. Zhou V, Agle K, Chen X, Beres A, Komorowski R, Belle L, et al. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease. J Clin Invest. 2016;126:3541-55 pubmed publisher
    ..Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10-regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. ..
  6. Wang M, Zhong D, Zheng Y, Li H, Chen H, Ma S, et al. Damage effect of interleukin (IL)-23 on oxygen-glucose-deprived cells of the neurovascular unit via IL-23 receptor. Neuroscience. 2015;289:406-16 pubmed publisher
    ..These results not only help us better understand the role of IL-23/IL-23R in brain ischemia, but also provide a potential therapeutic target in stroke. ..
  7. Lee Y, Awasthi A, Yosef N, Quintana F, Xiao S, Peters A, et al. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol. 2012;13:991-9 pubmed publisher
    ..Moreover, TGF-?3-induced T(H)17 cells were functionally and molecularly distinct from TGF-?1-induced T(H)17 cells and had a molecular signature that defined pathogenic effector T(H)17 cells in autoimmune disease. ..
  8. Ermann J, Staton T, Glickman J, de Waal Malefyt R, Glimcher L. Nod/Ripk2 signaling in dendritic cells activates IL-17A-secreting innate lymphoid cells and drives colitis in T-bet-/-.Rag2-/- (TRUC) mice. Proc Natl Acad Sci U S A. 2014;111:E2559-66 pubmed publisher
    ..Our data provide insight into the complex network of interactions between IL-17A-secreting ILCs and other components of the innate immune system in the development of colitis. ..
  9. Lee J, Tato C, Joyce Shaikh B, Gulen M, Gulan F, Cayatte C, et al. Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability. Immunity. 2015;43:727-38 pubmed publisher
    ..These results suggest that IL-17-producing ?? T cells are important for the maintenance and protection of epithelial barriers in the intestinal mucosa. ..
  10. Shih V, Cox J, Kljavin N, Dengler H, Reichelt M, Kumar P, et al. Homeostatic IL-23 receptor signaling limits Th17 response through IL-22-mediated containment of commensal microbiota. Proc Natl Acad Sci U S A. 2014;111:13942-7 pubmed publisher
    ..Thus, barrier defects generate a systemic environment that facilitates Th17 development. ..
  11. Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature. 2013;496:513-7 pubmed publisher
  12. Meyer zu Horste G, Wu C, Wang C, Cong L, Pawlak M, Lee Y, et al. RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression. Cell Rep. 2016;16:392-404 pubmed publisher
    ..We thus find that Notch signaling influences the development of pathogenic and non-pathogenic Th17 cells by reciprocally regulating IL-23R and IL-10 expression. ..
  13. Quiniou C, Domínguez Punaro M, Cloutier F, Erfani A, Ennaciri J, Sivanesan D, et al. Specific targeting of the IL-23 receptor, using a novel small peptide noncompetitive antagonist, decreases the inflammatory response. Am J Physiol Regul Integr Comp Physiol. 2014;307:R1216-30 pubmed publisher
  14. Malik S, Sadhu S, Elesela S, Pandey R, Chawla A, Sharma D, et al. Transcription factor Foxo1 is essential for IL-9 induction in T helper cells. Nat Commun. 2017;8:815 pubmed publisher
    ..The transcription factor Foxo1 can control regulatory T cell and Th1 function. Here the authors show that Foxo1 is also critical for IL-9 production by Th9 cells and other IL-9-producing cells. ..
  15. Kara E, McKenzie D, Bastow C, Gregor C, Fenix K, Ogunniyi A, et al. CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells. Nat Commun. 2015;6:8644 pubmed publisher
    ..Thus, our data identify a unique cell surface signature, trafficking mechanism and T-cell intrinsic regulators of GM-CSF/IFNγ-producing Th17 cells. ..
  16. Banerjee A, Bhattacharya P, Dagur P, Karmakar S, Ismail N, Joshi A, et al. Live Attenuated Leishmania donovani Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model. J Immunol. 2018;200:163-176 pubmed publisher
    ..This study unveiled the role of IL-23-dependent IL-17 induction in LdCen-/- parasite-induced immunity and subsequent protection against visceral leishmaniasis. ..
  17. Singh T, Zhang H, Borek I, Wolf P, Hedrick M, Singh S, et al. Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation. Nat Commun. 2016;7:13581 pubmed publisher
    ..Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells. ..
  18. Peters A, Pitcher L, Sullivan J, Mitsdoerffer M, Acton S, Franz B, et al. Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity. 2011;35:986-96 pubmed publisher
    ..Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ. ..
  19. Krausgruber T, Schiering C, Adelmann K, Harrison O, Chomka A, Pearson C, et al. T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine. Nat Commun. 2016;7:11627 pubmed publisher
    ..Our study identifies T-bet as a key modulator of IL-23-driven colitogenic responses in the intestine and has important implications for understanding of heterogeneity among inflammatory bowel disease patients. ..
  20. Sefik E, Geva Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire A, et al. MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of ROR?? regulatory T cells. Science. 2015;349:993-7 pubmed publisher
    ..Ror?, and the T(regs) that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Ror? results in very different outcomes even in closely related cell types. ..
  21. Yang J, Xu L. Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis. Med Sci Monit. 2016;22:2785-92 pubmed
    ..Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of inflammatory bowel diseases. ..
  22. Aychek T, Mildner A, Yona S, Kim K, Lampl N, Reich Zeliger S, et al. IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology. Nat Commun. 2015;6:6525 pubmed publisher
    ..Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology. ..
  23. Schiering C, Krausgruber T, Chomka A, Fröhlich A, Adelmann K, Wohlfert E, et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature. 2014;513:564-568 pubmed publisher
  24. Li H, Hsu H, Wu Q, Yang P, Li J, Luo B, et al. IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and ROR?t. Nat Commun. 2014;5:4259 pubmed publisher
    ..These results extend the action of IL-23 beyond its peripheral effects to a unique role in TCR-mediated negative selection including elimination of natural T regulatory cells in the thymus. ..
  25. Guo W, Luo C, Wang C, Zhu Y, Wang X, Gao X, et al. Protection against Th17 cells differentiation by an interleukin-23 receptor cytokine-binding homology region. PLoS ONE. 2012;7:e45625 pubmed publisher
  26. Riol Blanco L, Ordovas Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, et al. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature. 2014;510:157-61 pubmed publisher
    ..These findings indicate that TRPV1(+)Nav1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses. ..
  27. Chaudhry A, Samstein R, Treuting P, Liang Y, Pils M, Heinrich J, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34:566-78 pubmed publisher
    ..Thus, Treg cells limit Th17 cell inflammation by serving as principal amplifiers of negative regulatory circuits operating in immune effector cells. ..
  28. Kishi Y, Kondo T, Xiao S, Yosef N, Gaublomme J, Wu C, et al. Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity. J Exp Med. 2016;213:2489-2501 pubmed
    ..PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells. ..
  29. Duhen R, Glatigny S, Arbelaez C, Blair T, Oukka M, Bettelli E. Cutting edge: the pathogenicity of IFN-γ-producing Th17 cells is independent of T-bet. J Immunol. 2013;190:4478-82 pubmed publisher
    ..Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell-mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-γ expression in Th1 and Th17 cells. ..
  30. Grivennikov S, Wang K, Mucida D, Stewart C, Schnabl B, Jauch D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491:254-8 pubmed publisher
    ..We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth...
  31. Morishima N, Mizoguchi I, Takeda K, Mizuguchi J, Yoshimoto T. TGF-beta is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. Biochem Biophys Res Commun. 2009;386:105-10 pubmed publisher
    ..These results suggest that the induction of IL-23R and Th17 differentiation by IL-6 and IL-23 is mediated through endogenously produced TGF-beta. ..
  32. Chognard G, Bellemare L, Pelletier A, Domínguez Punaro M, Beauchamp C, Guyon M, et al. The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation. PLoS ONE. 2014;9:e89092 pubmed publisher
  33. Du F, Garg A, Kosar K, Majumder S, Kugler D, Mir G, et al. Inflammatory Th17 Cells Express Integrin ?v?3 for Pathogenic Function. Cell Rep. 2016;16:1339-1351 pubmed publisher
    ..Hence, integrin ?3 is required for Th17 cell-mediated autoimmune CNS inflammation. ..
  34. Kyttaris V, Zhang Z, Kuchroo V, Oukka M, Tsokos G. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol. 2010;184:4605-9 pubmed publisher
    ..The presented experiments document the importance of IL-23R-mediated signaling in the development of lupus nephritis and urge the consideration of proper biologics for the treatment of the disease. ..
  35. Purwar R, Schlapbach C, Xiao S, Kang H, Elyaman W, Jiang X, et al. Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells. Nat Med. 2012;18:1248-53 pubmed publisher
    ..These results suggest a role for IL-9 in tumor immunity and offer insight into potential therapeutic strategies. ..
  36. Franke M, Schröder J, Monhasery N, Ackfeld T, Hummel T, Rabe B, et al. Human and Murine Interleukin 23 Receptors Are Novel Substrates for A Disintegrin and Metalloproteases ADAM10 and ADAM17. J Biol Chem. 2016;291:10551-61 pubmed publisher
    ..Finally, interaction studies identified domains 1 and 3 of the IL-23R as the main ADAM17 binding sites. In summary, we describe human and murine IL-23R as novel targets for protein ectodomain shedding by ADAM10 and ADAM17. ..
  37. Haas J, Nistala K, Petermann F, Saran N, Chennupati V, Schmitz S, et al. Expression of miRNAs miR-133b and miR-206 in the Il17a/f locus is co-regulated with IL-17 production in ?? and ?? T cells. PLoS ONE. 2011;6:e20171 pubmed publisher
    ..Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions. ..
  38. Liang D, Zuo A, Shao H, Born W, O Brien R, Kaplan H, et al. IL-23 receptor expression on ?? T cells correlates with their enhancing or suppressive effects on autoreactive T cells in experimental autoimmune uveitis. J Immunol. 2013;191:1118-25 pubmed publisher
    ..The expression of variable IL-23R levels allows ?? T cells to have different regulatory effects on adaptive immune responses, conceivably as a result of ?? and ?? T cells competing for IL-23. ..
  39. Newcomb D, Cephus J, Boswell M, Fahrenholz J, Langley E, Feldman A, et al. Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma. J Allergy Clin Immunol. 2015;136:1025-34.e11 pubmed publisher
    ..17β-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men. ..
  40. Eken A, Singh A, Treuting P, Oukka M. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism. Mucosal Immunol. 2014;7:143-54 pubmed publisher
    ..Collectively, our results reveal that similar to its controversial role during chronic or adaptive colitis, IL-22 may also have opposite roles in innate colitis pathogenesis in a context and insult-dependent manner. ..
  41. Yang Y, Torchinsky M, Gobert M, Xiong H, Xu M, Linehan J, et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature. 2014;510:152-6 pubmed publisher
    ..These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines. ..
  42. Wang C, Yosef N, Gaublomme J, Wu C, Lee Y, Clish C, et al. CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity. Cell. 2015;163:1413-27 pubmed publisher
    ..Our study identifies CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells. ..
  43. Punkenburg E, Vogler T, Büttner M, Amann K, Waldner M, Atreya R, et al. Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer. Gut. 2016;65:1139-50 pubmed publisher
    ..Batf-dependent IL-23R(+) T cells represent a potential future therapeutic target limiting CRC progression. ..
  44. Singh A, Eken A, Fry M, Bettelli E, Oukka M. DOCK8 regulates protective immunity by controlling the function and survival of ROR?t+ ILCs. Nat Commun. 2014;5:4603 pubmed publisher
    ..Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of ROR?t(+) ILCs. ..
  45. Aden K, Rehman A, Falk Paulsen M, Secher T, Kuiper J, Tran F, et al. Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation. Cell Rep. 2016;16:2208-2218 pubmed publisher
    ..The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells. ..
  46. Yoon J, Leyva Castillo J, Wang G, Galand C, Oyoshi M, Kumar L, et al. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med. 2016;213:2147-66 pubmed publisher
    ..We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD. ..
  47. Wang C, Wu L, Bulek K, Martin B, Zepp J, Kang Z, et al. The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90. Nat Immunol. 2013;14:72-81 pubmed publisher
    ..In the absence of IL-17 signaling, IL-22 was the main contributor to skin inflammation, which provides a molecular mechanism for the association of Act1(D10N) with psoriasis susceptibility. ..
  48. Langowski J, Zhang X, Wu L, Mattson J, Chen T, Smith K, et al. IL-23 promotes tumour incidence and growth. Nature. 2006;442:461-5 pubmed
    ..We show that IL-23 is an important molecular link between tumour-promoting pro-inflammatory processes and the failure of the adaptive immune surveillance to infiltrate tumours. ..
  49. Grifka Walk H, Giles D, Segal B. IL-12-polarized Th1 cells produce GM-CSF and induce EAE independent of IL-23. Eur J Immunol. 2015;45:2780-6 pubmed publisher
    ..These data provide definitive evidence that autoimmune disease can be driven by distinct CD4(+) T-helper-cell subsets and polarizing factors. ..
  50. Floss D, Mrotzek S, Klöcker T, Schröder J, Grötzinger J, Rose John S, et al. Identification of canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the intracellular domain of the interleukin 23 receptor. J Biol Chem. 2013;288:19386-400 pubmed publisher
    ..In summary, we characterized IL-23-dependent signal transduction with a focus on STAT3 phosphorylation and identified canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the IL-23R. ..
  51. Laird R, Wolf B, Princiotta M, Hayes S. ?? T cells acquire effector fates in the thymus and differentiate into cytokine-producing effectors in a Listeria model of infection independently of CD28 costimulation. PLoS ONE. 2013;8:e63178 pubmed publisher
    ..Together, these data not only demonstrate an enhanced glucose metabolism in ?? T cells but also provide an explanation for why ?? T cells are less dependent on CD28 costimulation than ?? T cells. ..