CD38 and extracellular NAD+ regulate the development and maintenance of Hp vaccine‐induced CD4+ TRM in the gastric epithelium

IF 7.9 2区医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-10-01 DOI:10.1016/j.mucimm.2024.06.011

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Abstract

Tissue-resident memory T cells (T_RM) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4⁺ T_RM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of T_RM. Cluster of differentiation (CD)38 regulated mitochondrial activity and enhanced transforming growth factor-β signal transduction to promote the differentiation and residence of gastric epithelial CD4⁺ T_RM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of T_RM in gastric epithelium by the P2X7 receptor (P2RX7). Vitamin D3 and Gram-positive enhancer matrix (GEM) particles as immune adjuvants combined with Hp vaccination promoted the production of CD69⁺CD103⁺CD4⁺ T_RM.

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CD38 和细胞外 NAD+ 可调节胃上皮细胞中由 Hp 疫苗诱导的 CD4+ TRM 的发育和维持。

组织驻留记忆T细胞（TRM）可由感染和疫苗接种诱导，并在维持针对粘膜病原体的长期保护性免疫中发挥关键作用。我们的研究探讨了影响幽门螺杆菌（Hp）疫苗诱导的胃上皮CD4+TRM分化、成熟和稳定驻留的关键因素和机制，并优化了Hp疫苗接种，以促进TRM的产生和驻留。CD38通过介导CD105的表达，调节线粒体活性并增强TGF-β信号转导，从而促进胃上皮CD4+TRM的分化和驻留。细胞外核苷酸通过P2RX7影响TRM在胃上皮的长期维持。维生素D3和革兰氏阳性增强基质颗粒（GEMs）作为免疫佐剂与Hp疫苗接种结合可促进CD69+CD103+CD4+TRM的产生。

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来源期刊

Mucosal Immunology 医学-免疫学

CiteScore

16.60

自引率

3.80%

发文量

100

审稿时长

12 days

期刊介绍： Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.