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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

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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451561/
https://www.ncbi.nlm.nih.gov/pubmed/32853219
http://dx.doi.org/10.1371/journal.pone.0238070
Descripción
Sumario: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 SIRPγ(low) T-cells in RRMS and T1D positively correlated with proinflammatory molecules from T-cells. Finally, we show that SIRPγ(low) 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.