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. 2023 Nov;37(11):e23242.
doi: 10.1096/fj.202300462RR.

TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming

Chun-Hsien Chu  1   2 , Jia-Shing Chen  3 , Ya-Ling Chan  4 , Wei-Jen Lu  1 , Yi-Te Huang  5 , Pin-Cheng Mao  1 , Chun-I Sze  6 , H Sunny Sun  1   2
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TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming

Chun-Hsien Chu et al. FASEB J. 2023 Nov.

Abstract

TIAM Rac1-associated GEF 2 short form (TIAM2S) as an oncoprotein alters the immunity of peripheral immune cells to construct an inflammatory tumor microenvironment. However, its role in the activation of microglia, the primary innate immune cells of the brain, and neuroinflammation remains unknown. This study investigated the mechanism underlying TIAM2S shapes immune properties of microglia to facilitate neuron damage. Human microglial clone 3 cell line (HMC3) and human brain samples were applied to determine the presence of TIAM2S in microglia by western blots and double immunostaining. Furthermore, TIAM2S transgenic mice combined with multiple reconstituted primary neuron-glial culture systems and a cytokine array were performed to explore how TIAM2S shaped immune priming of microglia and participated in lipopolysaccharide (LPS)-induced neuron damage. TIAM2S protein was detectable in HMC3 cells and presented in a small portion (~11.1%) of microglia in human brains referred to as TIAM2S-positive microglia. With the property of secreted soluble factor-mediated immune priming, TIAM2S-positive microglia enhanced LPS-induced neuroinflammation and neural damage in vivo and in vitro. The gain- and loss-of-function experiments showed soluble intercellular adhesion molecule-1 (sICAM-1) participated in neurotoxic immune priming of TIAM2S+ microglia. Together, this study demonstrated a novel TIAM2S-positive microglia subpopulation enhances inflammation and neurotoxicity through sICAM-1-mediated immune priming.

Keywords: TIAM2S; immune priming; microglia; sICAM-1.

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References

REFERENCES

    1. Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol. 2005;6:167-180.
    1. Chiu CY, Leng S, Martin KA, Kim E, Gorman S, Duhl DM. Cloning and characterization of T-cell lymphoma invasion and metastasis 2 (TIAM2), a novel guanine nucleotide exchange factor related to TIAM1. Genomics. 1999;61:66-73.
    1. Mertens AE, Roovers RC, Collard JG. Regulation of Tiam1-Rac signalling. FEBS Lett. 2003;546:11-16.
    1. Chen JS, Su IJ, Leu YW, Young KC, Sun HS. Expression of T-cell lymphoma invasion and metastasis 2 (TIAM2) promotes proliferation and invasion of liver cancer. Int J Cancer. 2012;130:1302-1313.
    1. Chan YL, Lai WC, Chen JS, et al. TIAM2S mediates serotonin homeostasis and provokes a pro-inflammatory immune microenvironment permissive for colorectal tumorigenesis. Cancers (Basel). 2020;12:1844.

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