A T cell extrinsic mechanism by which IL-2 dampens Th17 differentiation.
Genetic variants in il2 and il2ra have been associated with autoimmune disease susceptibility in both genome-wide association studies (GWAS) in humans and in genetic linkage studies in experimental models of autoimmunity. Specifically, genetic variants resulting in a low IL-2 phenotype are susceptibility alleles while variants resulting in a high IL-2 phenotype are resistance alleles. The association of high IL-2 phenotypes with resistance has been attributed primarily to the T cell intrinsic promotion of regulatory T cell development, maintenance, and function; however, IL-2 can also act T cell intrinsically to dampen differentiation of pathogenic IL-17-producing Th17 cells. Here, we have uncovered a novel T cell extrinsic mechanism whereby IL-2 promotes both IFN-γ and IL-27 production from tissue resident macrophages which in turn dampen the differentiation of pathogenic Th17 cells.
Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: aanderson@rics.bwh.harvard.edu.
Ana C
AC
Anderson
Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Jenna M
JM
Sullivan
Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Dewar J
DJ
Tan
Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
David H
DH
Lee
Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: vkuchroo@evergrande.hms.harvard.edu.
Vijay K
VK
Kuchroo
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D064094:Interleukin-27 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D023421:Models, Animal; D011110:Polymorphism, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
D007376:Interleukin-2; D064094:Interleukin-27; D007371:Interferon-gamma
Cytokines; IL-17; Macrophages; T cells