Purpose: to review the function and genetics of killer immunoglobulin-like receptors (KIRs) and studies of KIR genetic associations with uveitis.
Methods: Review of published studies.
Results: KIRs are receptors on NK and some T cells. They may inhibit or activate cellular function, such as cytotoxicity and cytokine production. Studies have been published examining KIR gene associations with birdshot chorioretinopathy (BCR), Vogt-Koyanagi-Harada (VKH) disease, and HLA-B27-associated acute anterior uveitis (AAU) and axial spondyloarthropathy. Evidence for increased activating and/or less inhibitory KIR and HLA gene combinations was found for BCR and VKH disease. In HLA-B27-associated disease, a trend toward decreased activation and stronger inhibition was found, except for the weakly inhibitory 3DL1 and Bw4(T80) combination. This latter combination was also found to confer risk in BCR.
Conclusions: KIR genetics are complex, as are the functions of KIR-bearing cells. Nonetheless, evidence for KIRs in the pathogenesis of uveitis has been found.
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http://dx.doi.org/10.3109/09273948.2010.538798 | DOI Listing |
Biomedicines
January 2025
Immunology Service, Clinical University Hospital Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette-Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. : We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls.
View Article and Find Full Text PDFAm J Reprod Immunol
February 2025
GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
Problem: Natural killer (NK) cells undergo education for full functionality via interactions between killer immunoglobulin-like receptors (KIRs) or NKG2A and human leukocyte antigen (HLA) ligands. Presumably, education is important during early pregnancy as insufficient education has been associated with impaired vascular remodeling and restricted fetal growth in mice. NK cell education is influenced by receptor co-expression patterns, human cytomegalovirus (CMV), the HLA-E107 dimorphism, and HLA-B leader peptide variants.
View Article and Find Full Text PDFInnate Immun
January 2025
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Background: Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients.
View Article and Find Full Text PDFReprod Med Biol
January 2025
Department of Obstetrics and Gynecology School of Medicine, Hyogo Medical University Nishinomiya Hyogo Japan.
Background: Uterine endometrial natural killer (uNK) cells represent major leukocytes in the mid-secretory phase of the cell cycle, and their number is further increased during early pregnancy. The activating and inhibitory receptors expressed on their surface mediate various functions of uNK cells, such as cytotoxicity, cytokine production, spiral artery remodeling, and self-recognition.
Methods: This study reviewed the most recent information (PubMed database, 175 articles included) regarding the activating and inhibitory receptors on uNK cells in human females with healthy pregnancies and the evidence indicating their significance in various reproductive failures.
Nat Immunol
January 2025
Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.
Here we analyzed the relative contributions of CD4 regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8 regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4 and CD8 regulatory T cells. Using CRISPR-Cas9 gene editing, we were able to achieve a reduction of ~90-95% in the expression of these genes.
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