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- Title
Altered expression of SIRPγ on the T-cells of relapsing remitting multiple sclerosis and type 1 diabetes patients could potentiate effector responses from T-cells.
- Authors
Sinha, Sushmita; Renavikar, Pranav S.; Crawford, Michael P.; Steward-Tharp, Scott M.; Brate, Ashley; Tsalikian, Eva; Tansey, Michael; Shivapour, Ezzatollah T.; Cho, Tracey; Kamholz, John; Karandikar, Nitin J.
- Abstract
Factors regulating self-antigen directed immune-responses in autoimmunity are poorly understood. Signal regulatory protein gamma (SIRPγ) is a human T-cell specific protein with genetic variants associated with type 1 diabetes (T1D). SIRPγ's function in the immune system remains unclear. We show that T1D and relapsing remitting multiple sclerosis (RRMS) subjects have significantly greater frequency of rs2281808 T genetic variant, that correlates with reduced SIRPγ-expression in T-cells. Importantly, reduced SIRPγ-expression in RRMS and T1D subjects was not restricted to T variant, suggesting SIRPγ-expression is also regulated by disease specific factors in autoimmunity. Interestingly, increased frequencies of SIRPγlow T-cells in RRMS and T1D positively correlated with proinflammatory molecules from T-cells. Finally, we show that SIRPγlow T-cells have enhanced pathogenecity in vivo in a GVHD model. These findings suggest that decreased-SIRPγ expression, either determined by genetic variants or through peripherally acquired processes, may have a mechanistic link to autoimmunity through induction of hyperactive T-cells.
- Subjects
TYPE 1 diabetes; T cells; MULTIPLE sclerosis; PEOPLE with diabetes; ALEMTUZUMAB; NATALIZUMAB
- Publication
PLoS ONE, 2020, Vol 15, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0238070