.png){kind=icon}
Return
Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes
.png){kind=icon}
OA
AI
DOI：10.1371/journal.pgen.1011456.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Inhibitory killer cell immunoglobulin-like receptors (iKIRs) are a family of inhibitory receptors that are expressed by natural killer (NK) cells and late-stage differentiated T cells. There is accumulating evidence that iKIRs regulate T cell-mediated immunity. Recently, we reported that T cell-mediated control was enhanced by iKIRs in chronic viral infections. We hypothesized that in the context of autoimmunity, where an enhanced T cell response might be considered detrimental, iKIRs would have an opposite effect. We studied Type 1 diabetes (T1D) as a paradigmatic example of autoimmunity. In T1D, variation in the Human Leucocyte Antigen (HLA) genes explains up to 50% of the genetic risk, indicating that T cells have a major role in T1D etiopathogenesis. To investigate if iKIRs affect this T cell response we asked whether HLA associations were modified by iKIR genes. We conducted an immunogenetic analysis of a case-control T1D dataset (N = 11,961) and found that iKIR genes, in the presence of genes encoding their ligands, have a consistent and significant effect on protective HLA class II genetic associations. Our results were validated in an independent data set. We conclude that iKIRs significantly decrease HLA class II protective associations and suggest that iKIRs regulate CD4+ T cell responses in T1D.
Keywords:
LYMPHOID TYROSINE PHOSPHATASE
IMMUNOGLOBULIN-LIKE RECEPTOR
GENOME-WIDE ASSOCIATION
KILLER-CELL RECEPTORS
T-CELLS
GENETIC SUSCEPTIBILITY
C LIGAND
NK CELLS
KIR3DL2
RESISTANCE
Journal
IF:
3.7
Papers:
9.8K
Citations:
4.6W
Organization
View more organizations
Cited Papers
ShareSaveA Leishmania major protein with extensive homology to silent information regulator 2 of Saccharomyces cerevisiae.png)
Gene
GeneIF0
PREAI
ShareSaveTreatment patterns among patients with moderate-to-severe ulcerative colitis in the United States and EuropePLOS ONEOAAI
PLOS ONEIF0
OAAIShareSaveKIR haplotypes are associated with late-onset type 1 diabetes in European-American familiesGENES AND IMMUNITYOAAI
GENES AND IMMUNITYIF4.5
OAAIShareSaveShareSaveFactors Influencing T Cell Activation and Programmed Death 1 Expression in HIV-Infected Children
PREAI
ShareSaveShareSave View more