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

Sushmita Sinha; Pranav S Renavikar; Michael P Crawford; Scott M Steward-Tharp; Ashley Brate; Eva Tsalikian; Michael Tansey; Ezzatollah T Shivapour; Tracey Cho; John Kamholz; Nitin J Karandikar

doi:10.1371/journal.pone.0238070

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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

Journal article

Open access

Peer reviewed

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

Sushmita Sinha, Pranav S Renavikar, Michael P Crawford, Scott M Steward-Tharp, Ashley Brate, Eva Tsalikian, Michael Tansey, Ezzatollah T Shivapour, Tracey Cho, John Kamholz, …

PloS one, Vol.15(8), pp.e0238070-e0238070

2020

DOI: 10.1371/journal.pone.0238070

PMCID: PMC7451561

PMID: 32853219

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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.

Adult

Alleles

Animals

Antigens, Differentiation - genetics

Autoimmunity

Case-Control Studies

Diabetes Mellitus, Type 1 - genetics

Diabetes Mellitus, Type 1 - immunology

Female

Gene Expression Regulation

Genotype

Humans

Male

Mice

Middle Aged

Multiple Sclerosis - genetics

Multiple Sclerosis - immunology

Polymorphism, Single Nucleotide

Receptors, Immunologic - genetics

Recurrence

T-Lymphocytes - immunology

T-Lymphocytes - metabolism

Young Adult

Details

Title: Subtitle: 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
Creators: Sushmita Sinha - University of Iowa
Pranav S Renavikar - University of Iowa
Michael P Crawford - University of Iowa
Scott M Steward-Tharp - University of Iowa
Ashley Brate - University of Iowa
Eva Tsalikian - University of Iowa
Michael Tansey - University of Iowa
Ezzatollah T Shivapour - University of Iowa
Tracey Cho - University of Iowa
John Kamholz - University of Iowa
Nitin J Karandikar - University of Iowa
Resource Type: Journal article
Publication Details: PloS one, Vol.15(8), pp.e0238070-e0238070
DOI: 10.1371/journal.pone.0238070
PMID: 32853219
PMCID: PMC7451561
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: T90 DE023520 / NIDCR NIH HHS R01 AI092106 / NIAID NIH HHS
Language: English
Date published: 2020
Academic Unit: Neurology; Endocrinology and Diabetes; Psychiatry; Oral Pathology, Radiology and Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Dental Research
Record Identifier: 9984186485202771

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