Anti-inflammatory activities of IL-37b on atopic dermatitis via regulating AMPK- mTOR and intestinal metabolites-dependent autophagy
Refereed conference paper presented and published in conference proceedings



摘要Background : Interaction between eosinophils and dermal fibroblasts is essential for allergic inflammation in atopic dermatitis (AD). Autophagy plays a vital role in regulating immunity via distinct intracellular signaling mechanism.

Method : Human eosinophil and dermal fibroblast co- culture with AD- related cytokine IL- 31/IL- 33 stimulation, and MC903- induced AD murine model were employed to investigate the anti-inflammatory mechanism of regulatory IL- 1 family cytokine IL- 37, by using the perspective of molecular biology, intestinal bacterial diversity and metabolites.

Results : IL- 37 inhibited IL- 6, CXCL8, CXCL9 and CXCL10 production in vitro , and upregulated autophagy- related LC3B and AMP- activated protein kinase (AMPK) and down- regulated mammalian target of rapamycin (mTOR) expression in vitro and in vivo . In CRISPR/Cas9 human IL- 37b knock- in mice, IL- 37b could also decrease ear tissue swelling and the expression of inflammatory cytokines and chemokines including IL- 4, CCL2, IL- 17A and transforming growth factor- β, itching sensation and eosinophil infiltration. Furthermore, IL- 37b could indirectly enhance in vivo autophagy by regulating intestinal metabolites such as 3- methyladenine, adenosine monophosphate and 2- hydroxyglutarate, and suppress inflammation by inhibiting innate immune response via the modulation of intestinal metabolite cholic acid and gut microbiota.

Conclusion : In summary, IL- 37b could significantly ameliorate eosinophils- mediated allergic inflammation by enhancing its autophagy and suppressing inflammatory response via regulating intestinal bacteria and their metabolites in AD. Results therefore suggest IL- 37 is a promising anti- inflammatory cytokine for AD treatment.
著者Chun Kwok Wong, Tianheng Hou, K.L. Hon, Peiyong Jiang, Miranda Sin-Man Tsang
會議名稱European Academy of Allergy and Clinical Immunology Digital Congress
會議地點London - Hybrid
期次Suppl 109
頁次27 - 27

上次更新時間 2022-15-01 於 00:36