Waiming Cheng , Meihong He , Elfira Jurat , Luoyi Jin , Shunchang Luo , Zerong Guan , Yingying Zeng , Xianghong Wang , Jianlei Hao , Xin Tang , Haiyan Zhu , Zhinan Yin , Hengwen Yang
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引用次数: 0
Abstract
Psoriasis is associated with gut microbiota dysbiosis and aberrantly elevated histamine levels, yet the pathological role of microbiota-derived histamine remains unclear. In this study, colonization of mice with histamine-producing engineered E. coli (BL21_pET-17b_hdc) revealed that microbiota-derived histamine (non-dietary origin) significantly exacerbated skin inflammation in a psoriasis model and induced γδT17 cell expansion across multiple immune organs. These effects were abolished in γδT cell-deficient mice. RNA sequencing demonstrated that histamine exposure upregulated the histamine receptor gene Hrh1 and activated the Wnt signaling pathway via pathway enrichment analysis. Further in vitro experiments confirmed that histamine promoted γδT17 cell differentiation in an Hrh1 receptor-dependent manner, with this process being associated with Wnt pathway activity. Our findings elucidate that gut microbiota-derived histamine exacerbates psoriatic inflammation by coordinately regulating the Hrh1 receptor and Wnt signaling pathway to drive γδT17 cell differentiation, providing a theoretical foundation for therapeutic strategies targeting microbial metabolites.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.