This week Science published interesting study showing cooperation between prostaglandin E2 (PGE2), one of the most abundantly produced prostaglandin, and innate lymphoid cell (ILC3)-produced IL-22 in keeping gut barrier tight during systemic inflammation (e.g. bacteremia, sepsis, and septic shock).
This is very neatly done study. In the initial experiments, the authors showed that pre-treatment of mice with indomethacin (which suppresses PGE2 production) increased their susceptibility to systemic inflammation following endotoxin (LPS) injection.
Interestingly, when mice were also pre-treated with EP4 agonist (PGE2 receptor), it reduced systemic inflammation following LPS injection.
Moreover, beneficial effect of EP4 agonist on systemic inflammation following LPS injection was mimicked by antibiotic pre-treatment, suggesting the role of gut barrier in protection mediated by PGE2.
Indeed, EP4 agonist pre-treatment prevented bacterial translocation from gut into sterile internal tissues such as liver.
Finally, the authors showed that PGE2-EP4 signaling in group 3 innate lymphoid cells was necessary for IL-22 production that contributed to maintaining gut barrier function during systemic inflammation (of note, EP4 agonist had (a) no effect in IL-22KO mice and it was still active in (b) RAG KO mice that lack adaptive immune system).
In summary, this study provided additional support for innate cell-derived IL-22 as a cytokine necessary for keeping gut tissue in healthy condition.
David Usharauli
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