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LILRB receptor-mediated regulation of myeloid cell maturation and function

  • Focussed Research Review
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Abstract

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.

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Abbreviations

ANGPTL:

Angiopoietin-like

BCR:

B cell receptor

BST2:

Bone marrow stromal cell Ag 2

Btk:

Bruton’s tyrosine kinase

DAG:

Diacylglycerol

DCs:

Dendritic cells

ERK:

Extracellular signal-regulated kinase

FHC:

Free heavy chain

HIV:

Human immunodeficiency virus

HLA:

Human leukocyte antigen

IP3:

Inositol triphosphate

ITAM:

Immunoreceptor tyrosine-based activating motif

ITIM:

Immunoreceptor tyrosine-based inhibitory motif

KIR:

Killer cell inhibitory receptor

LAT:

Linker for activation of T cells

LILR:

Leukocyte immunoglobulin-like receptor

LILRA:

Leukocyte immunoglobulin-like receptor subfamily A

LILRB:

Leukocyte immunoglobulin-like receptor subfamily B

MAG:

Myelin-associated glycoprotein

MAPK:

Mitogen-activated protein kinase

MDSC:

Myeloid-derived suppressor cell

MHC-I:

Major histocompatibility complex I

NF-κB:

Nuclear factor-κB

NFAT:

Nuclear factor of activated T cells

NK:

Natural killer

OMgp:

Oligodendrocyte–myelin glycoprotein

PI3K:

PI3-kinase

Syk:

Spleen tyrosine kinase

TCR:

T cell receptor

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Acknowledgements

The authors thank Ms. Marcia Meseck for editing the manuscript. This work was supported in part by grants from the National Cancer Institute to S.-H. Chen (R01CA109322, R01CA127483, and R01 CA 208703) and to P.-Y. Pan (R01CA140243 and R01 CA188610).

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Authors and Affiliations

  1. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA

    William van der Touw, Hui-Ming Chen, Ping-Ying Pan & Shu-Hsia Chen

  2. Immunotherapy Research Center, Houston Methodist Research institute, 6670 Bertner Ave, Houston, TX, 77030, USA

    Hui-Ming Chen, Ping-Ying Pan & Shu-Hsia Chen

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  1. William van der Touw
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  4. Shu-Hsia Chen
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Correspondence to Shu-Hsia Chen.

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This paper is a Focussed Research Review based on a presentation given at the conference Regulatory Myeloid Suppressor Cells: From Basic Discovery to Therapeutic Application which was hosted by the Wistar Institute in Philadelphia, PA, USA, 16th–19th June, 2016. It is part of a Cancer Immunology, Immunotherapy series of Focussed Research Reviews.

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van der Touw, W., Chen, HM., Pan, PY. et al. LILRB receptor-mediated regulation of myeloid cell maturation and function. Cancer Immunol Immunother 66, 1079–1087 (2017). https://doi.org/10.1007/s00262-017-2023-x

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  • DOI: https://doi.org/10.1007/s00262-017-2023-x

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