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qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
Published on: March 6, 2019
A 17q12 allele is associated with altered NK cell subsets and function
Zongqi Xia1, Qingquan Liu, Christoph T Berger
1Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, MA 02115, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|February 21, 2012
Summary
The rs9916629(C) allele influences natural killer (NK) cell populations in the blood, decreasing cytotoxic CD56(dim) cells and increasing regulatory CD56(bright) cells. This genetic variation impacts NK cell function, potentially affecting immunity to infection and autoimmunity.
Area of Science:
- Immunology
- Genetics
- Cell Biology
Background:
- Natural killer (NK) cells are crucial for innate immunity.
- A prior genome-wide association study linked the 17q12 allele rs9916629(C) to reduced peripheral blood NK cell counts.
- The specific impact of this polymorphism on NK cell subsets and functions remained unclear.
Purpose of the Study:
- To validate the association between the rs9916629 polymorphism and NK cell frequency.
- To identify specific NK cell subpopulations and functions affected by the rs9916629 polymorphism.
- To explore potential molecular mechanisms underlying these observed differences.
Main Methods:
- Replication of a genome-wide association study using a cohort of 96 healthy adults.
- Targeted multiparameter flow cytometry to analyze NK cell phenotypes and functions.
- Transcriptional profiling of NK cells to investigate gene expression changes.
Main Results:
- The rs9916629(C) allele was associated with a lower frequency of CD56(dim) NK cells and a higher frequency of CD56(bright) NK cells.
- An increased proportion of NK cells expressing the inhibitory NKG2A receptor was observed with the rs9916629(C) allele.
- Functional assays showed decreased macrophage inflammatory protein-1β secretion and increased degranulation in response to specific stimuli for the rs9916629(C) allele.
- rs9916629 influences transcription factors like TBX21, impacting NK cell differentiation.
Conclusions:
- The rs9916629(C) allele is validated to alter NK cell proportions in peripheral blood.
- This polymorphism skews NK cells towards a specific phenotypic and functional profile, characterized by reduced cytotoxic potential and altered regulatory capacity.
- These findings suggest a potential role for rs9916629 in modulating the immune response to infections and autoimmune conditions.
