Peer-Reviewed Journal Details
Mandatory Fields
Russell, S. E.,Moore, A. C.,Fallon, P. G.,Walsh, P. T.
2012
Plos One
Soluble IL-2Ralpha (sCD25) exacerbates autoimmunity and enhances the development of Th17 responses in mice
Validated
Optional Fields
Animals Autoimmune Diseases/immunology/metabolism/pathology Autoimmunity Cell Differentiation *Encephalomyelitis, Autoimmune, Experimental/immunology/metabolism/pathology Humans Immunity, Cellular *Interleukin-2/immunology/metabolism *Interleukin-2 Receptor alpha Subunit/blood/immunology Mice Signal Transduction *Th17 Cells/immunology/metabolism
7
10
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.
1932-6203 (Electronic) 19
http://www.ncbi.nlm.nih.gov/pubmed/23077668
10.1371/journal.pone.0047748
Grant Details