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Neuropilin-1 expression distinguishes self-reactive helper T cells in systemic autoimmune disease


ABSTRACT: Pathogenic T helper cells (Th cells) that respond to self-antigen cannot be easily distinguished from beneficial Th cells. These cells can generate systemic autoimmune disease in response to widely-expressed self-antigens. In this study, we have identified Neuropilin-1 (NRP1) as a cell surface marker of self-reactive Th cells. NRP1+ Th cells, absent in non-regulatory T cell subsets in normal mice, appeared in models of systemic autoimmune disease and strongly correlated with disease symptoms. NRP1+ Th cells were greatly reduced in Nr4a2 cKO mice, which have reduced self-reactive responses but showed normal responses against exogenous antigens. Transfer of NRP1+ Th cells was sufficient to initiate or accelerate systemic autoimmune disease; and targeting NRP1-expressing Th cells therapeutically ameliorated SLE-like autoimmune symptoms in BXSB-Yaa mice. Peripheral NRP1+ Th cells were significantly increased in human SLE patients. Our data suggest that self-reactive Th cells can be phenotypically distinguished within the Th cell pool. These findings offer a novel approach to identify self-reactive Th cells and target them to treat systemic autoimmune disease.

SUBMITTER: Dr. Ben, JE Raveney 

PROVIDER: S-SCDT-EMM-2022-15864 | biostudies-other |

REPOSITORIES: biostudies-other

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