In:
PeerJ, PeerJ, Vol. 11 ( 2023-09-26), p. e15976-
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.
Type of Medium:
Online Resource
ISSN:
2167-8359
DOI:
10.7717/peerj.15976/fig-1
DOI:
10.7717/peerj.15976/fig-2
DOI:
10.7717/peerj.15976/fig-3
DOI:
10.7717/peerj.15976/fig-4
DOI:
10.7717/peerj.15976/fig-5
DOI:
10.7717/peerj.15976/supp-1
DOI:
10.7717/peerj.15976/supp-2
DOI:
10.7717/peerj.15976/supp-3
DOI:
10.7717/peerj.15976/supp-4
Language:
English
Publisher:
PeerJ
Publication Date:
2023
detail.hit.zdb_id:
2703241-3