Effect of anti-in ammatory IL-37 on ameliorating atopic dermatitis via enhancing autophagy-dependent AMPK-mTOR signaling pathway
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AbstractInteraction between eosinophils and dermal fibroblasts is essential for allergic inflammation in atopic dermatitis (AD). IL-37 is reported to alleviate inflammation by regulating AMPK-mTOR signaling, which is a key regulator of autophagy. Human eosinophils (EOS) and dermal fibroblast (HDF) co-culture system was used for cytokine-chemokine secretion and autophagy related protein expression investigation upon IL-31/IL-33 stimuli. IL-37 knock-in (KI) mice were bred for AD model. Ear swelling, EOS infiltration, serum and lesional ear cytokines, spleen regulatory T (Treg) cell and autophagy-related proteins were assessed in vivo. Snatching times were recorded to evaluate itching severity. IL-37 significantly inhibited IL-6 and CXCL8 production, meanwhile upregulated LC3B and AMPK and down-regulated mTOR expression. However, no autophagy process was detected in either EOS or HDF alone culture. Ear swelling of KI was reduced 10. 8 and 15. 3% at Day 15 and 17, and EOS number in ear of KI was signifi¬cantly lower than that of WT. Importantly, IL-37 signi¬ficantly ameliorated itching sensation. The LC3B and AMPK protein expressions were significantly increased, while p62 and mTOR expressions were significantly decreased in ear of KI compared with WT. TNF-a, IL-17A and CCL5 genes were higher expressed in WT than that in KI. IL-5, IL-6 and IL-17 levels in serum of KI was much lower, while Treg cells in spleen of KI was much higher compared with WT. IL-37 could signifi¬cantly alleviate AD symptom by inhibiting eosinophil infiltration as well as eosinophils-mediated allergic inflammation via autophagy mechanism. It suggests that IL-37 could be a promising anti-inflammatory agent for AD.
All Author(s) ListTianheng Hou, Xiaoyu Sun, Kam Lun Ellis Hon, Jing Zhu, Wai Kei Christopher Lam, Chun-Kwok Wong
Name of ConferenceThe 48th Annual Meeting of The Japanese Society for Immunology
Start Date of Conference11/12/2019
End Date of Conference13/12/2019
Place of ConferenceJapan
Country/Region of ConferenceJapan
Proceedings TitleProceedings of the Japanese Society for Immunology (JSI)
Year2019
Month12
Volume Number48
PublisherThe Japanese Society for Immunology
Place of PublicationJapan
Article number3-D-W17-8-P
Pages495
ISSN0919-1984
LanguagesEnglish-United Kingdom

Last updated on 2020-27-11 at 15:37