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

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

SUBMITTER: Li Z 

PROVIDER: S-EPMC7052276 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature