title: Interleukin-6 expands homeostatic space for peripheral T cells.
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.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Changwan
authors.initials: C
authors.lastname: Hong
authors.forename: Anna S
authors.initials: AS
authors.lastname: Nam
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Keller
authors.forename: Davinna L
authors.initials: DL
authors.lastname: Ligons
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hee-Won
authors.initials: HW
authors.lastname: Yoon
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Park
authors.forename: Megan A
authors.initials: MA
authors.lastname: Luckey
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008136:Longevity / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains; D015850:Interleukin-6; C577686:interleukin-6, mouse
keywords: Apoptosis; Cytokine; Proliferation; Survival; Thymus