| Title: | Intestinal dysbiosis exacerbates skin inflammation via microbial metabolite-driven Th2 cell differentiation |
| Journal: | Immunity |
| Published: | 16 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41997160/ |
| DOI: | https://doi.org/10.1016/j.immuni.2026.03.019 |
Publication 17974
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Abstract
The interplay between gut microbiota and the mucosal immune system critically regulates systemic immunity and disease susceptibility. Here, we demonstrate that intestinal epithelial Toll-like receptor (TLR)4 deficiency reshaped the gut microbiome and subsequently exacerbated atopic dermatitis (AD) in mice. Mechanistically, TLR4 deficiency reduced Akkermansia muciniphila abundance and enriched choline trimethylamine-lyase (CutC)-expressing bacteria. This enhanced microbial choline-to-trimethylamine conversion and elevated circulating trimethylamine oxide (TMAO) levels. Clinically, AD patients exhibited increased plasma TMAO levels that positively correlated with disease severity and immunoglobulin E (IgE) levels. UK Biobank data also showed that higher dietary choline intake was associated with increased AD risk. TMAO promoted T helper (Th)2 differentiation by directly interacting with protein phosphatase 5 (PPP5) and enhancing PPP5-mediated dephosphorylation of PPARγ. CD4+ T cell-specific PPARγ deletion abolished TMAO-driven skin pathology in AD mice. Our results reveal intestinal dysbiosis, as a result of innate immune deficiency, as a driver of inflammatory Th2 cells and AD pathology, highlighting a link among the gut immune environment, microbial metabolites, and skin disease.</p>
21 Authors
- Lu Yu
- Shuying Peng
- Xi Chen
- Tianxing Wu
- Lijun Dong
- Jialiang Luo
- Shuangbin Xu
- Jia Zhou
- Xiaoshan Zhao
- Lei Zheng
- Gang Shu
- Xuemin Wang
- Liping Huang
- Qingyun Chen
- Deke Jiang
- Liang-Dan Sun
- Phillip Hylemon
- Xiang-Yang Wang
- Ledong Sun
- Li Ma
- Daming Zuo
1 Application
| Application ID | Title |
|---|---|
| 90369 | Analysis of the Dynamic Characteristics of Aging-related Serum Uric Acid in Nervous and Digestive System Disorders with Machine Learning Methods |
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