Abstract
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.
References
Feb 1, 1996·The Journal of Experimental Medicine·C TeuscherK S Tung
Apr 26, 2000·Genome Research·P A LyonsJ A Todd
Apr 16, 2004·Cell·Cecile KingNora Sarvetnick
Sep 3, 2004·Nature Reviews. Immunology·Thomas R Malek, Allison L Bayer
Oct 4, 2005·Nature Immunology·Heon ParkChen Dong
Aug 15, 2006·Nature Immunology·Marcel BattenNico Ghilardi
Feb 6, 2007·Nature Genetics·Jun YamanouchiPere Santamaria
Mar 17, 2007·Immunity·Arian LaurenceJohn J O'shea
Nov 13, 2007·Nature Immunology·Amit AwasthiHoward L Weiner
Nov 13, 2007·Nature Immunology·Denise C FitzgeraldAbdolmohamad Rostami
Nov 13, 2007·Nature Immunology·Jason S StumhoferChristopher A Hunter
Nov 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Helen M McGuireCecile King
Sep 20, 2011·The American Journal of Pathology·Hirokazu FujimotoKoichi Node
Oct 25, 2011·The Journal of Clinical Investigation·Sue M LiuVijay K Kuchroo
Dec 24, 2011·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Koen Vandenbroeck
Jul 4, 2012·Nature Immunology·Francisco J QuintanaVijay K Kuchroo
Sep 18, 2012·Immunity·Aisling O'Hara HallChristopher A Hunter
Citations
Mar 31, 2016·Clinical Reviews in Allergy & Immunology·Yaxiong DengQianjin Lu
Aug 13, 2015·Clinical Reviews in Allergy & Immunology·Yu-Qing XieZhe-Xiong Lian
Dec 21, 2017·Scientific Reports·Qi TanHong Wang
Mar 17, 2017·Clinical Reviews in Allergy & Immunology·Andrea T BorchersM Eric Gershwin
Oct 16, 2016·Journal of Immunotherapy·Maggie L DillerMandy L Ford
Nov 12, 2015·Frontiers in Immunology·Prenitha Mercy Ignatius Arokia DossManu Rangachari
Apr 3, 2021·American Journal of Human Genetics·Minal CaliskanJoseph C Maranville