Journal
EMBO REPORTS
Volume 21, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/embr.201949332
Keywords
ectonucleotide pyrophosphatase; phosphodiesterase family member 2; ENPP2; inflammatory bowel diseases; lipid raft; toll-like receptor 4
Categories
Funding
- Oakland University
- National Institutes of Health [DK079015]
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [2019R1A2C1010536]
- National Research Foundation of Korea [2019R1A2C1010536] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Autotaxin (ATX) converts lysophosphatidylcholine and sphingosyl-phosphorylcholine into lysophosphatidic acid and sphingosine 1-phosphate, respectively. Despite the pivotal function of ATX in lipid metabolism, mechanisms by which ATX regulates immune and inflammatory disorders remain elusive. Here, using myeloid cell lineage-restricted Atx knockout mice, we show that Atx deficiency disrupts membrane microdomains and lipid rafts, resulting in the inhibition of Toll-like receptor 4 (TLR4) complex formation and the suppression of adaptor recruitment, thereby inhibiting TLR4-mediated responses in macrophages. Accordingly, TLR4-induced innate immune functions, including phagocytosis and iNOS expression, are attenuated in Atx-deficient macrophages. Consequently, Atx(-/-)mice exhibit a higher bacterial prevalence in the intestinal mucosa compared to controls. When combined with global Il10(-/-)mice, which show spontaneous colitis due to the translocation of luminal commensal microbes into the mucosa, myeloid cell lineage-restricted Atx knockout accelerates colitis development compared to control littermates. Collectively, our data reveal that Atx deficiency compromises innate immune responses, thereby promoting microbe-associated gut inflammation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available