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

Sci Rep 2018 10 18;8(1):15440. Epub 2018 Oct 18.

Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA.

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.

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http://www.nature.com/articles/s41598-018-33901-1
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http://dx.doi.org/10.1038/s41598-018-33901-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194019PMC
October 2018
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References

(Supplied by CrossRef)

JC Barrett et al.
Nature genetics 2009

AK Kiani et al.
Diabetes research and clinical practice 2015

MV Reddy et al.
Genes and immunity 2011

AN Barclay et al.
Nature reviews. Immunology 2006

L Piccio et al.
Blood 2005

M Stefanidakis et al.
Blood 2008

IS Gabrielsen et al.
Human molecular genetics 2016

FZ Chowdhury et al.
PloS one 2014

JJ Knox et al.
Frontiers in immunology 2014

LM McLane et al.
Journal of immunology 2013

SH Fu et al.
Journal of biomedical science 2017

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