van der Touw William, Chen Hui-Ming, Pan Ping-Ying, Chen Shu-Hsia
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
Immunotherapy Research Center, Houston Methodist Research institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
Cancer Immunol Immunother. 2017 Aug;66(8):1079-1087. doi: 10.1007/s00262-017-2023-x. Epub 2017 Jun 21.
The leukocyte immunoglobulin-like receptor (LILR) family comprises a set of paired immunomodulatory receptors expressed among human myeloid and lymphocyte cell populations. While six members of LILR subfamily A (LILRA) associate with membrane adaptors to signal via immunoreceptor tyrosine-based activating motifs (ITAM), LILR subfamily B (LILRB) members signal via multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM). Ligand specificity of some LILR family members has been studied in detail, but new perspective into the immunoregulatory aspects of this receptor family in human myeloid cells has been limited. LILRB receptors and the murine ortholog, paired immunoglobulin-like receptor B (PIRB), have been shown to negatively regulate maturation pathways in myeloid cells including mast cells, neutrophils, dendritic cells, as well as B cells. Our laboratory further demonstrated in mouse models that PIRB regulated functional development of myeloid-derived suppressor cell and the formation of a tumor-permissive microenvironment. Based on observations from the literature and our own studies, our laboratory is focusing on how LILRs modulate immune homeostasis of human myeloid cells and how these pathways may be targeted in disease states. Integrity of this pathway in tumor microenvironments, for example, permits a myeloid phenotype that suppresses antitumor adaptive immunity. This review presents the evidence supporting a role of LILRs as myeloid cell regulators and ongoing efforts to understand the functional immunology surrounding this family.
白细胞免疫球蛋白样受体（LILR）家族由一组在人类髓系和淋巴细胞群体中表达的配对免疫调节受体组成。LILR亚家族A（LILRA）的六个成员与膜适配器结合，通过基于免疫受体酪氨酸的激活基序（ITAM）发出信号，而LILR亚家族B（LILRB）成员则通过多个基于免疫受体酪氨酸的抑制基序（ITIM）发出信号。一些LILR家族成员的配体特异性已得到详细研究，但关于该受体家族在人类髓系细胞免疫调节方面的新观点仍然有限。LILRB受体及其小鼠同源物配对免疫球蛋白样受体B（PIRB）已被证明对包括肥大细胞、中性粒细胞、树突状细胞以及B细胞在内的髓系细胞成熟途径具有负调节作用。我们实验室在小鼠模型中进一步证明，PIRB调节髓系来源抑制细胞的功能发育以及肿瘤允许性微环境的形成。基于文献观察和我们自己的研究，我们实验室专注于LILRs如何调节人类髓系细胞的免疫稳态，以及在疾病状态下这些途径如何成为靶点。例如，肿瘤微环境中该途径的完整性允许一种抑制抗肿瘤适应性免疫的髓系表型。这篇综述展示了支持LILRs作为髓系细胞调节因子作用的证据，以及为理解围绕该家族的功能免疫学所做的持续努力。
