Leukocyte immunoglobulin-like receptor subfamily B member 4

Definition:

Inhibitory receptor involved in the down-regulation of the immune response and the development of immune tolerance. Receptor for FN1. Receptor for apolipoprotein APOE. Receptor for ALCAM/CD166. Inhibits receptor-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions. Inhibits FCGR1A/CD64-mediated monocyte activation by inducing phosphatase-mediated down-regulation of the phosphorylation of multiple proteins including LCK, SYK, LAT and ERK, leading to a reduction in TNF production. This inhibition of monocyte activation occurs at least in part via binding to FN1. Inhibits T cell proliferation, inducing anergy, suppressing the differentiation of IFNG-producing CD8+ cytoxic T cells and enhancing the generation of CD8+ T suppressor cells. Induces up-regulation of CD86 on dendritic cells. Interferes with TNFRSF5-signaling and NF-kappa-B up-regulation.

References:

[1]. Mi Deng, et al. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature. 2018 Oct;562(7728):605-609. [Content Brief]

[2]. Zheng Xu, et al. ILT3.Fc-CD166 Interaction Induces Inactivation of p70 S6 Kinase and Inhibits Tumor Cell Growth. J Immunol. 2018 Feb 1;200(3):1207-1219. [Content Brief]

[3]. C C Chang, et al. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 2002 Mar;3(3):237-43. [Content Brief]

[4]. Mei-Tzu Su, et al. Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice. Int Immunol. 2021 Jul 23;33(8):447-458. [Content Brief]

[5]. M Cella, et al. A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing. J Exp Med. 1997 May 19;185(10):1743-51. [Content Brief]

[6]. Seunghee Kim-Schulze, et al. Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of Th anergy and differentiation of CD8+ T suppressor cells. J Immunol. 2006 Mar 1;176(5):2790-8. [Content Brief]

[7]. Hao Kim Lu, et al. Leukocyte Ig-like receptor B4 (LILRB4) is a potent inhibitor of FcgammaRI-mediated monocyte activation via dephosphorylation of multiple kinases. J Biol Chem. 2009 Dec 11;284(50):34839-48. [Content Brief]

[8]. Damien P Brown, et al. The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell phenotype and, along with LILRB2 (ILT4), is upregulated in response to Salmonella infection. BMC Immunol. 2009 Oct 27;10:56. [Content Brief]

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