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- Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis
- Su-Man Kim; Shinhye Park; Seung-Ho Hwang; Eun-Young Lee; Jong-Hwan Kim; Ga Seul Lee; G Lee; Dong-Ho Chang; Jae Geun Lee; Jungwon Hwang; Youngjin Lee; M Kyung; E K Kim; Jae-Hoon Kim; Tae-Hwan Kim; Jeong Hee Moon; Byoung Chan Kim; G Ko; Seon-Young Kim; J H Ryu; Jeong Soo Lee; Chul-Ho Lee; J Y Kim; S Kim; W J Lee; Myung Hee Kim
- Bibliographic Citation
- Cell Host & Microbe, vol. 31, no. 6, pp. 1021-1037
- Publication Year
- Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis.
- Elsevier-Cell Press
- Appears in Collections:
- Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
Division of Bio Technology Innovation > Core Research Facility & Analysis Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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