Tedla Nicodemus, Lee Chyh-Woei, Borges Luis, Geczy Carolyn L, Arm Jonathan P
Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia.
J Leukoc Biol. 2008 Feb;83(2):334-43. doi: 10.1189/jlb.0507314. Epub 2007 Nov 12.
The leukocyte Ig-like receptors (LILRs) comprise a family of cell-surface immunoregulatory receptors with activating and inhibitory members. The inhibitory LILRs possess cytoplasmic ITIMs that down-regulate signaling by nonreceptor tyrosine kinase cascades. The activating members have a truncated cytoplasmic domain and signal through the FcR gamma chain. We examined the expression of LILRs on human mast cells during their development in vitro. Progenitor mast cells expressed cell surface inhibitory LILRB1, -B2, -B3, and -B4 and activating LILRA1. However, although mature cord blood-derived mast cells (hMCs) had detectable mRNA encoding multiple LILRs, none were expressed on the cell surface. Culture of progenitor mast cells or hMCs with various cytokine combinations failed to retain or induce cell surface expression of the LILRs. It is interesting that hMCs expressed LILRB5 in cytoplasmic granules and upon cross-linking of the high-affinity IgE receptor, released LILRB5 into the culture medium. Our results demonstrate that LILRs are developmentally regulated in human mast cells and that LILRB5 is expressed in mast cell granules and the release of soluble LILRB5 following IgE FcR-dependent stimulation, which has potential for amplification of mast cell-dependent, inflammatory responses.
白细胞免疫球蛋白样受体（LILRs）是一类细胞表面免疫调节受体家族，包括激活型和抑制型成员。抑制型LILRs具有细胞质免疫受体酪氨酸抑制基序（ITIMs），可通过非受体酪氨酸激酶级联反应下调信号传导。激活型成员具有截短的细胞质结构域，并通过FcRγ链进行信号传导。我们研究了人肥大细胞在体外发育过程中LILRs的表达情况。祖肥大细胞表达细胞表面抑制型LILRB1、-B2、-B3和-B4以及激活型LILRA1。然而，尽管成熟的脐血来源肥大细胞（hMCs）有可检测到的编码多种LILRs的mRNA，但细胞表面均未表达。用各种细胞因子组合培养祖肥大细胞或hMCs未能保留或诱导LILRs的细胞表面表达。有趣的是，hMCs在细胞质颗粒中表达LILRB5，并且在高亲和力IgE受体交联后，将LILRB5释放到培养基中。我们的结果表明，LILRs在人肥大细胞中受到发育调控，并且LILRB5在肥大细胞颗粒中表达，以及在IgE FcR依赖性刺激后可溶性LILRB5的释放，这有可能放大肥大细胞依赖性炎症反应。
