TLR7 promotes skin inflammation via activating NFκB-mTORC1 axis in rosacea

PeerJ. 2023 Sep 26:11:e15976. doi: 10.7717/peerj.15976. eCollection 2023.

Abstract

Rosacea is a chronic inflammatory skin disease originated from damaged skin barrier and innate/adaptive immune dysregulation. Toll-like receptors (TLRs) sense injured skin and initiate downstream inflammatory and immune responses, whose role in rosacea is not fully understood. Here, via RNA-sequencing analysis, we found that the TLR signaling pathway is the top-ranked signaling pathway enriched in rosacea skin lesions, in which TLR7 is highlighted and positively correlated with the inflammation severity of disease. In LL37-induced rosacea-like mouse models, silencing TLR7 prevented the development of rosacea-like skin inflammation. Specifically, we demonstrated that overexpressing TLR7 in keratinocytes stimulates rapamycin-sensitive mTOR complex 1 (mTORC1) pathway via NFκB signaling. Ultimately, TLR7/NFκ B/mTORC1 axis promotes the production of cytokines and chemokines, leading to the migration of CD4+T cells, which are infiltrated in the lesional skin of rosacea. Our report reveals the crucial role of TLR7 in rosacea pathogenesis and indicatesa promising candidate for rosacea treatments.

Keywords: MTOR; NFκB; Rosacea; Skin immunology; Skin inflammation; TLR7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dermatitis* / metabolism
  • Inflammation / metabolism
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Rosacea* / metabolism
  • Skin
  • Toll-Like Receptor 7* / metabolism

Substances

  • NF-kappa B
  • Toll-Like Receptor 7
  • Tlr7 protein, mouse
  • Mechanistic Target of Rapamycin Complex 1

Associated data

  • figshare/10.6084/m9.figshare.22725614.v2

Grants and funding

This work was supported by the National Key Research and Development Program of China (No. 2021YFF1201200), the National Natural Science Funds for Distinguished Young Scholars (No. 82225039), the National Natural Science Foundation of China (No. 81874251, No. 82173448, No. 82073457), Natural Science Foundation of Hunan province, China (No. 2022JJ40201). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.