Altered expression of SIRP[gamma] on the T-cells of relapsing remitting multiple sclerosis and type 1 diabetes patients could potentiate effector responses from T-cells

• Published in: PloS one Vol. 15; no. 8; p. e0238070
• Main 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
• Format: Journal Article
• Language: English
• Published: Public Library of Science 27.08.2020
• Subjects: Development and progression; Genetic aspects; Health aspects; Multiple sclerosis; Recurrence (Disease); Signaling peptides and proteins; T cells; Type 1 diabetes; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0238070

Factors regulating self-antigen directed immune-responses in autoimmunity are poorly understood. Signal regulatory protein gamma (SIRP[gamma]) is a human T-cell specific protein with genetic variants associated with type 1 diabetes (T1D). SIRP[gamma]'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 SIRP[gamma]-expression in T-cells. Importantly, reduced SIRP[gamma]-expression in RRMS and T1D subjects was not restricted to T variant, suggesting SIRP[gamma]-expression is also regulated by disease specific factors in autoimmunity. Interestingly, increased frequencies of SIRP[gamma].sup.low T-cells in RRMS and T1D positively correlated with proinflammatory molecules from T-cells. Finally, we show that SIRP[gamma].sup.low T-cells have enhanced pathogenecity in vivo in a GVHD model. These findings suggest that decreased-SIRP[gamma] expression, either determined by genetic variants or through peripherally acquired processes, may have a mechanistic link to autoimmunity through induction of hyperactive T-cells.