Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41419-021-04357-5
Title: DOK3 maintains intestinal homeostasis by suppressing JAK2/STAT3 signaling and S100a8/9 production in neutrophils
Authors: Loh, Jia Tong
Lee, Koon-Guan
Lee, Alison P.
Teo, Joey Kay Hui
Lim, Hsueh Lee
Kim, Susana Soo-Yeon
Tan, Andy Hee-Meng
Lam, Kong-Peng 
Issue Date: 1-Nov-2021
Publisher: Springer Nature
Citation: Loh, Jia Tong, Lee, Koon-Guan, Lee, Alison P., Teo, Joey Kay Hui, Lim, Hsueh Lee, Kim, Susana Soo-Yeon, Tan, Andy Hee-Meng, Lam, Kong-Peng (2021-11-01). DOK3 maintains intestinal homeostasis by suppressing JAK2/STAT3 signaling and S100a8/9 production in neutrophils. Cell Death and Disease 12 (11) : 1054. ScholarBank@NUS Repository. https://doi.org/10.1038/s41419-021-04357-5
Rights: Attribution 4.0 International
Abstract: How pathogenesis of inflammatory bowel disease (IBD) depends on the complex interplay of host genetics, microbiome and the immune system is not fully understood. Here, we showed that Downstream of Kinase 3 (DOK3), an adapter protein involved in immune signaling, confers protection of mice from dextran sodium sulfate (DSS)-induced colitis. DOK3-deficiency promotes gut microbial dysbiosis and enhanced colitis susceptibility, which can be reversed by the transfer of normal microbiota from wild-type mice. Mechanistically, DOK3 exerts its protective effect by suppressing JAK2/STAT3 signaling in colonic neutrophils to limit their S100a8/9 production, thereby maintaining gut microbial ecology and colon homeostasis. Hence, our findings reveal that the immune system and microbiome function in a feed-forward manner, whereby DOK3 maintains colonic neutrophils in a quiescent state to establish a gut microbiome essential for intestinal homeostasis and protection from IBD. © 2021, The Author(s).
Source Title: Cell Death and Disease
URI: https://scholarbank.nus.edu.sg/handle/10635/232373
ISSN: 2041-4889
DOI: 10.1038/s41419-021-04357-5
Rights: Attribution 4.0 International
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