Soluble IL-2Rα (sCD25) exacerbates autoimmunity and enhances the development of Th17 responses in mice.
A strong association exists between mutations at the IL2 receptor alpha chain (CD25) gene locus and susceptibility to a number of T cell driven autoimmune diseases. Interestingly, the presence of certain CD25 susceptibility alleles has been correlated with significantly increased levels of the soluble form of CD25 (sCD25) in the serum of patients. However, the functional consequences, if any, of this observation are unknown. We have demonstrated that elevated levels of sCD25 in vivo resulted in exacerbated experimental autoimmune encephalomyelitis (EAE) and enhanced antigen-specific Th17 responses in the periphery. sCD25 exerted its effects early during the Th17 developmental programme in vitro, through inhibiting signalling downstream of the IL-2R. Although, sCD25 did not interact with the T cell surface, it specifically bound to secreted IL-2 demonstrating its ability to act as a decoy receptor for IL-2 in the T cell microenvironment. These data identify the ability of sCD25 to promote autoimmune disease pathogenesis and enhance Th17 responses through its ability to sequester local IL-2.
Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.
Shane E
SE
Russell
Anne C
AC
Moore
Padraic G
PG
Fallon
Patrick T
PT
Walsh
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology; D051379:Mice; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit