1. Current understanding on TREM-2 molecular biology and physiopathological functions.
- Author
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Bharadwaj, Shiv, Groza, Yaroslava, Mierzwicka, Joanna M., and Malý, Petr
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IMMUNOREGULATION , *MYELOID cells , *KILLER cells , *NATURAL immunity , *PHAGOCYTOSIS , *CELL physiology , *T cells , *MOLECULAR biology - Abstract
[Display omitted] • TREM-2 modulates both innate and adaptive immunity via pleotropic pathways. • TREM-2/DAP12/SYK-mediated pathways determines the fates of different cells. • TREM-2 level regulated by transcriptional, epigenetics, and posttranscriptional factors. • TREM-2 promote multifaceted immunosuppressive TME to support tumor progression. • Targeting TREM-2+TAMs enhance the anti-tumor immunity through CD8+ TILs function. Triggering receptor expressed on myeloid cells 2 (TREM-2), a glycosylated receptor belonging to the immunoglobin superfamily and especially expressed in the myeloid cell lineage, is frequently explained as a reminiscent receptor for both adaptive and innate immunity regulation. TREM-2 is also acknowledged to influence NK cell differentiation via the PI3K and PLCγ signaling pathways, as well as the partial activation or direct inhibition of T cells. Additionally, TREM-2 overexpression is substantially linked to cell-specific functions, such as enhanced phagocytosis, reduced toll-like receptor (TLR)-mediated inflammatory cytokine production, increased transcription of anti-inflammatory cytokines, and reshaped T cell function. Whereas TREM-2-deficient cells exhibit diminished phagocytic function and enhanced proinflammatory cytokines production, proceeding to inflammatory injuries and an immunosuppressive environment for disease progression. Despite the growing literature supporting TREM-2+ cells in various diseases, such as neurodegenerative disorders and cancer, substantial facets of TREM-2-mediated signaling remain inadequately understood relevant to pathophysiology conditions. In this direction, herein, we have summarized the current knowledge on TREM-2 biology and cell-specific TREM-2 expression, particularly in the modulation of pivotal TREM-2-dependent functions under physiopathological conditions. Furthermore, molecular regulation and generic biological relevance of TREM-2 are also discussed, which might provide an alternative approach for preventing or reducing TREM-2-associated deformities. At last, we discussed the TREM-2 function in supporting an immunosuppressive cancer environment and as a potential drug target for cancer immunotherapy. Hence, summarized knowledge of TREM-2 might provide a window to overcome challenges in clinically effective therapies for TREM-2-induced diseases in humans. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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