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Critical Reviews™ in Immunology
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ISSN Печать: 1040-8401
ISSN Онлайн: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2019029559
pages 479-489

Biological and Clinical Significance of Human NKRP1A/LLT1 Receptor/Ligand Interactions

Agata Bialoszewska
Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
Jacek Malejczyk
Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland

Краткое описание

Killer cell lectin-like receptors (KLRs) are C-type lectin-like glycoproteins encoded by genes clustered in the natural killer gene complex (NKC) located on the short arm of human chromosome 12. In addition to the NKG2 subfamily, the NKC includes a less characterized group of genes coding for NKRP1 receptors and their ligands of the C-type lectin (CLEC) subfamily. Among this group, the best recognized is the NKRP1A/LLT1 pair encoded respectively by the KLRB1 and CLEC2D genes. Both molecules are type II transmembrane-signaling glycoproteins with an extracellular C-type lectin domain. NKRP1A is predominantly expressed on NK cells, where it acts as an inhibitory receptor. However, it stimulates T cells, which results in release of IL-17 and inflammatory cytokines. Triggering LLT1 on NK cells stimulates IFN-γ production. Similarly, it stimulates activation of B cells. LLT1 is also expressed by osteoblasts and chondrocytes and inhibits bone degradation. Expression of LLT1 by tumor cells may facilitate their escape from NK cell surveillance. On the other hand, NKRP1A may be involved in activation of T and B lymphocytes in the course of inflammatory reactions and pathogenesis of autoimmune disorders. Thus, the NKRP1A/LLT1 receptor/ligand system appears to be a new therapeutic target that may be useful in the treatment of cancer as well as some autoinflammatory disorders.

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