Title | Interleukin-6 expands homeostatic space for peripheral T cells. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Hong C, Nam AS, Keller HR, Ligons DL, Park J-Y, Yoon H-W, Park JJ, Luckey MA, Park J-H |
Journal | Cytokine |
Volume | 64 |
Issue | 2 |
Pagination | 532-40 |
Date Published | 2013 Nov |
ISSN | 1096-0023 |
Keywords | Animals, Cell Cycle, Cell Proliferation, Cell Survival, Homeostasis, Immunoglobulin Heavy Chains, Interleukin-6, Longevity, Mice, Mice, Inbred C57BL, Signal Transduction, T-Lymphocytes, Thymocytes |
Abstract | T cell homeostasis and survival is dependent on interleukin-7 (IL-7). Immune activation, however, downregulates IL-7 receptor expression on T cells so that T cell survival during activation must be maintained independently of IL-7. The pro-inflammatory cytokine IL-6 shares common signaling pathways with IL-7 and can promote T cell survival in vitro. But whether IL-6 promotes T cell survival and homeostasis in vivo is not clear. Notably, IL-6 overexpression results in massive plasmacytosis and autoimmunity so that an IL-6 effect on in vivo T cell survival has remained untested. To overcome this limitation, here we generated IL-6 transgenic mice on an immunoglobulin heavy chain (IgH) deficient background which rendered them B cell deficient. Notably, such IgH(KO)IL6(Tg) mice were free of any signs of inflammation or autoimmunity and remained healthy throughout the course of analysis. In these mice, we found that IL-6 overexpression significantly increased peripheral T cell numbers, but importantly without increasing thymopoiesis. Moreover, IL-6 signaled T cells maintained their naïve phenotype and did not express activation/memory markers, suggesting that increased T cell numbers were due to increased T cell survival and not because of expansion of activated T cells. Mechanistically, we found that IL-6 signaling induced expression of pro-survival factors Mcl-1 and Pim-1/-2 but not Bcl-2. Thus, IL-6 is a T cell homeostatic cytokine that expands T cell space and can maintain the naïve T cell pool. |
DOI | 10.1016/j.cyto.2013.08.001 |
Alternate Journal | Cytokine |
PubMed ID | 23988623 |
PubMed Central ID | PMC3806195 |
Grant List | ZIA BC011214-03 / / Intramural NIH HHS / United States ZIA BC011214-04 / / Intramural NIH HHS / United States ZIA BC011215-03 / / Intramural NIH HHS / United States ZIA BC011215-04 / / Intramural NIH HHS / United States |
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