IL-6 Promotes T Cell Proliferation and Expansion under Inflammatory Conditions in Association with Low-Level RORγt Expression

• Published in: The Journal of immunology (1950) 2018-11, Vol.201 (10), p.2934-2946
• Main Authors: Li, Bofeng, Jones, Lindsay L, Geiger, Terrence L
• Format: Article
• Language: English
• Subjects: Animals; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; Cell Proliferation - physiology; Gene Expression Regulation - immunology; Homeostasis - immunology; Inflammation - immunology; Interleukin-6 - immunology; Lymphocyte Activation - immunology; Mice; Mice, Knockout; Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Th17 Cells - cytology; Th17 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1800016

IL-6 is a critical driver of acute and chronic inflammation and has been reported to act as a T cell survival factor. The influence of IL-6 on T cell homeostasis is not well resolved. We demonstrate that IL-6 signaling drives T cell expansion under inflammatory conditions but not during normal homeostasis. During inflammation, IL-6Rα-deficient T cells are unable to effectively compete with wild type T cells. IL-6 promotes T cell proliferation, and this is associated with low-level expression of the RORγt transcription factor. T cells upregulate mRNA at levels substantially diminished from that seen in Th17 cells. Blockade of RORγt through genetic knockout or a small molecule inhibitor leads to T cell expansion defects comparable to those in IL-6Rα-deficient T cells. Our results indicate that IL-6 plays a key role in T cell expansion during inflammation and implicates a role for the transient induction of low-level RORγt.