Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes.
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-medi...
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Public Library of Science (PLoS)
2024-12-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011456 |
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| author | Laura Mora-Bitria Bisrat J Debebe Kelly L Miners Kristin Ladell Charandeep Kaur James A Traherne Wei Jiang David A Price Linda Hadcocks Nicholas A R McQuibban John Trowsdale F Susan Wong Nikolas Pontikos Christoph Niederalt Becca Asquith |
| author_facet | Laura Mora-Bitria Bisrat J Debebe Kelly L Miners Kristin Ladell Charandeep Kaur James A Traherne Wei Jiang David A Price Linda Hadcocks Nicholas A R McQuibban John Trowsdale F Susan Wong Nikolas Pontikos Christoph Niederalt Becca Asquith |
| author_sort | Laura Mora-Bitria |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-404475003cfa482f8cacf699ff1cb2e9 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-404475003cfa482f8cacf699ff1cb2e92025-08-20T03:10:47ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042024-12-012012e101145610.1371/journal.pgen.1011456Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes.Laura Mora-BitriaBisrat J DebebeKelly L MinersKristin LadellCharandeep KaurJames A TraherneWei JiangDavid A PriceLinda HadcocksNicholas A R McQuibbanJohn TrowsdaleF Susan WongNikolas PontikosChristoph NiederaltBecca AsquithInhibitory 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.https://doi.org/10.1371/journal.pgen.1011456 |
| spellingShingle | Laura Mora-Bitria Bisrat J Debebe Kelly L Miners Kristin Ladell Charandeep Kaur James A Traherne Wei Jiang David A Price Linda Hadcocks Nicholas A R McQuibban John Trowsdale F Susan Wong Nikolas Pontikos Christoph Niederalt Becca Asquith Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes. PLoS Genetics |
| title | Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes. |
| title_full | Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes. |
| title_fullStr | Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes. |
| title_full_unstemmed | Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes. |
| title_short | Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes. |
| title_sort | inhibitory kirs decrease hla class ii mediated protection in type 1 diabetes |
| url | https://doi.org/10.1371/journal.pgen.1011456 |
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