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

• 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: United States Public Library of Science 27.08.2020; Public Library of Science (PLoS)
• Subjects: Adult; Age; Alleles; Animals; Antibodies; Antigens; Antigens, Differentiation - genetics; Autoantigens; Autoimmune diseases; Autoimmunity; Biology and Life Sciences; Case-Control Studies; Cell adhesion & migration; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Disease; Effector cells; Female; Gene Expression Regulation; Genetic diversity; Genetic variance; Genotype; Graft-versus-host reaction; Humans; Immune system; Inflammation; Lymphocytes T; Male; Medical research; Medicine and Health Sciences; Mice; Middle Aged; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Neurology; Pathology; Pediatrics; Polymorphism, Single Nucleotide; Proteins; Receptors, Immunologic - genetics; Recurrence; Research and Analysis Methods; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Young Adult; United States > US; Iowa; Iowa City Iowa
• 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 (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.