The linker for activation of B cells (LAB)/Non-T Cell Activation Linker (NTAL) regulates triggering receptor expressed on myeloid cells (TREM)-2 signaling and macrophage Inflammatory responses independently of the linker for activation of T cells

Whittaker, Gillian C., Orr, Selinda Jane, Quigley, Laura, Hughes, Laurel, Francischetti, Ivo M. B., Zhang, Weigou and McVicar, Daniel W. 2010. The linker for activation of B cells (LAB)/Non-T Cell Activation Linker (NTAL) regulates triggering receptor expressed on myeloid cells (TREM)-2 signaling and macrophage Inflammatory responses independently of the linker for activation of T cells. Journal of Biological Chemistry 285 (5) , pp. 2976-2985. 10.1074/jbc.M109.038398

Full text not available from this repository.

Abstract

Triggering receptor expressed on myeloid cells-2 (TREM-2) is rapidly emerging as a key regulator of the innate immune response via its regulation of macrophage inflammatory responses. Here we demonstrate that proximal TREM-2 signaling parallels other DAP12-based receptor systems in its use of Syk and Src-family kinases. However, we find that the linker for activation of T cells (LAT) is severely reduced as monocytes differentiate into macrophages and that TREM-2 exclusively uses the linker for activation of B cells (LAB encoded by the gene Lat2−/−) to mediate downstream signaling. LAB is required for TREM-2-mediated activation of Erk1/2 and dampens proximal TREM-2 signals through a novel LAT-independent mechanism resulting in macrophages with proinflammatory properties. Thus, Lat2−/− macrophages have increased TREM-2-induced proximal phosphorylation, and lipopolysaccharide stimulation of these cells leads to increased interleukin-10 (IL-10) and decreased IL-12p40 production relative to wild type cells. Together these data identify LAB as a critical, LAT-independent regulator of TREM-2 signaling and macrophage development capable of controlling subsequent inflammatory responses.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Uncontrolled Keywords:	Immunology; Immunology/Innate Immunity; Receptors/Leukocyte/Lymphocyte; Signal Transduction/Adapter Proteins; Signal Transduction/Phosphotyrosine; Signal Transduction/Phosphotyrosine/SH2 Domains; Macrophage
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	04 Jun 2017 05:06
URI:	https://orca.cardiff.ac.uk/id/eprint/48541

Citation Data

Cited 25 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item