Bialoszewska Agata, Malejczyk Jacek
Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
Crit Rev Immunol. 2018;38(6):479-489. doi: 10.1615/CritRevImmunol.2019029559.
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.
杀伤细胞凝集素样受体（KLRs）是一类C型凝集素样糖蛋白，由位于人类12号染色体短臂上的自然杀伤基因复合体（NKC）中的基因簇编码。除了NKG2亚家族外，NKC还包括一组特征较少的基因，这些基因编码NKRP1受体及其C型凝集素（CLEC）亚家族的配体。在这一组中，最广为人知的是分别由KLRB1和CLEC2D基因编码的NKRP1A/LLT1对。这两种分子都是具有细胞外C型凝集素结构域的II型跨膜信号糖蛋白。NKRP1A主要在自然杀伤细胞上表达，在那里它作为一种抑制性受体发挥作用。然而，它会刺激T细胞，导致白细胞介素-17和炎性细胞因子的释放。激活自然杀伤细胞上的LLT1会刺激γ干扰素的产生。同样，它也会刺激B细胞的活化。LLT1也由成骨细胞和软骨细胞表达，并抑制骨降解。肿瘤细胞表达LLT1可能有助于它们逃避自然杀伤细胞的监视。另一方面，NKRP1A可能参与炎症反应过程中T和B淋巴细胞的活化以及自身免疫性疾病的发病机制。因此，NKRP1A/LLT1受体/配体系统似乎是一个新的治疗靶点，可能对癌症以及某些自身炎症性疾病的治疗有用。
