An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells

Sushmita Sinha; Nicholas Borcherding; Pranav S Renavikar; Michael P Crawford; Eva Tsalikian; Michael Tansey; Ezzatollah T Shivapour; Frank Bittner; John Kamholz; Heena Olalde; Emilee Gibson; Nitin J Karandikar

doi:10.1038/s41598-018-33901-1

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An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells

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An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells

Sushmita Sinha, Nicholas Borcherding, Pranav S Renavikar, Michael P Crawford, Eva Tsalikian, Michael Tansey, Ezzatollah T Shivapour, Frank Bittner, John Kamholz, Heena Olalde, …

Scientific reports, Vol.8(1), pp.15440-9

10/18/2018

DOI: 10.1038/s41598-018-33901-1

PMCID: PMC6194019

PMID: 30337675

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Abstract

Multiple GWAS studies have shown that the SNP rs2281808 TT variant, present within the SIRPG gene, is associated with autoimmune diseases, such as type 1 diabetes. However, the role of SIRPγ in human T-cells is not known, neither is the functional significance of TT variant. Here we investigated SIRPG genotypes and their effects on the fate and function of human T-cells. We found that the presence of T variant resulted in reduction of SIRPγ expression on T-cells. Functionally, SIRPγ CD8 T-cells in CT and TT individuals existed in a heightened effector state with lower activation threshold and had greater expression of genes and molecules associated with migratory and cytotoxic potential. Further, SIRPγ CD8 T-cells were deficient in transcription factors associated with long-term functional memory formation. Our study reveals biological consequences of the SNP rs2281808 and provides novel insights into the potential mechanisms by which SIRPγ might regulate human immune responses.

T-Lymphocyte Subsets - immunology

Receptors, Immunologic - physiology

Lymphocyte Activation

Humans

Middle Aged

Gene Expression Regulation

Autoimmunity - genetics

Genotype

Male

Antigens, Differentiation - physiology

Antigens, Differentiation - biosynthesis

Receptors, Immunologic - biosynthesis

T-Lymphocyte Subsets - metabolism

CD8-Positive T-Lymphocytes - metabolism

Adult

Female

Aged

Antigens, Differentiation - genetics

Polymorphism, Single Nucleotide

CD8-Positive T-Lymphocytes - immunology

Receptors, Immunologic - genetics

Immunologic Memory - genetics

Cytotoxicity, Immunologic

Details

Title: Subtitle: An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells
Creators: Sushmita Sinha - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA. Sushmita-sinha@uiowa.edu
Nicholas Borcherding - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Pranav S Renavikar - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Michael P Crawford - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Eva Tsalikian - Department of Pediatrics, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Michael Tansey - Department of Pediatrics, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Ezzatollah T Shivapour - Department of Neurology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Frank Bittner - Department of Neurology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
John Kamholz - Department of Neurology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Heena Olalde - Department of Neurology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Emilee Gibson - Department of Neurology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Nitin J Karandikar - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.8(1), pp.15440-9
DOI: 10.1038/s41598-018-33901-1
PMID: 30337675
PMCID: PMC6194019
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: R01AI121567 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01 AI121567 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 10/18/2018
Academic Unit: Dermatology; Neurology; Endocrinology and Diabetes; Psychiatry; Stead Family Department of Pediatrics; Pathology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984093340802771

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