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A T cell extrinsic mechanism by which IL-2 dampens Th17 differentiation.

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-? and IL-27 production from tissue resident macrophages which in turn dampen the differentiation of pathogenic Th17 cells.

SUBMITTER: Anderson AC

PROVIDER: S-EPMC4414806 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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A T cell extrinsic mechanism by which IL-2 dampens Th17 differentiation.

Anderson Ana C AC Sullivan Jenna M JM Tan Dewar J DJ Lee David H DH Kuchroo Vijay K VK

Journal of autoimmunity 20150226

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 pr ...[more]

PMID: 25725581

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