title: Committed Tc17 cells are phenotypically and functionally resistant to the effects of IL-27.
abstract: IL-17-secreting CD8(+) T cells (Tc17 cells) have been implicated in immunity to infections, cancer, and autoimmune diseases. Thus far, studies on Tc17 cells have primarily investigated their development from naïve precursors, while the biology of committed Tc17 cells has been less characterized, in particular during the effector phase of immune responses. IL-27 is an important regulator of inflammation through the induction of regulatory Tr1 cells, as well as a suppressor of Th17-cell development. IL-27 suppresses the development of Tc17 cells, but its effects on committed Tc17 cells are unknown. Here we demonstrate that even though IL-27 completely inhibited the development of C57BL/6 mouse Tc17 cells, it had little effect on previously committed Tc17 cells. Although committed Tc17 cells were capable of responding to IL-27, it had no effect on expression of RORγt and RORα, or production of various cytokines. Committed Tc17 cells did not express granzyme B and lacked cytotoxicity in vitro, features that remained unaltered by IL-27 treatment. Nonetheless, they efficiently induced diabetes, irrespective of treatment with IL-27 prior to transfer into RIP-mOVA mice. These findings suggest that use of IL-27 to modulate autoimmune diseases might have limited therapeutic efficacy if autoaggressive Tc17 cells have already developed.
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Mohamed
authors: M
authors: El-Behi
authors: Hong
authors: H
authors: Dai
authors: Joao G
authors: JG
authors: Magalhaes
authors: Daniel
authors: D
authors: Hwang
authors: Guang-Xian
authors: GX
authors: Zhang
authors: Abdolmohamad
authors: A
authors: Rostami
authors: Bogoljub
authors: B
authors: Ciric
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D064094:Interleukin-27 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D064094:Interleukin-27
keywords: Diabetes; IL-23; IL-27; Lineage; Tc17