LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells

Zunling Li, Mi Deng, Fangfang Huang, Changzhu Jin, Shuang Sun, Heyu Chen, Xiaoye Liu, Licai He, Ali H. Sadek, Cheng Cheng Zhang

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We recently demonstrated that leukocyte Ig-like receptor 4 (LILRB4) expressed by monocytic acute myeloid leukemia (AML) cells mediates T-cell inhibition and leukemia cell infiltration via its intracellular domain. The cytoplasmic domain of LILRB4 contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs); the tyrosines at positions 360, 412, and 442 are phosphorylation sites. Here, we analyzed how the ITIMs of LILRB4 in AML cells mediate its function. Our in vitro and in vivo data show that Y412 and Y442, but not Y360, of LILRB4 are required for T-cell inhibition, and all three ITIMs are needed for leukemia cell infiltration. We constructed chimeric proteins containing the extracellular domain of LILRB4 and the intracellular domain of LILRB1 and vice versa. The intracellular domain of LILRB4, but not that of LILRB1, mediates T-cell suppression and AML cell migration. Our studies thus defined the unique signaling roles of LILRB4 ITIMs in AML cells.

Original languageEnglish (US)
Pages (from-to)272-282
Number of pages11
JournalCellular and Molecular Immunology
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2020

Keywords

  • AML
  • ITIM motifs
  • LILRB4
  • T cell suppression
  • infiltration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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