AbstractSjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis.

摘要Sjögren综合征（SS）是一种自身免疫性疾病，其特征是唾液腺和泪腺中的慢性炎症浸润。粘膜相关不变T（MAIT）细胞是先天性T细胞的一个子集，主要存在于粘膜组织中，在上皮稳态中起着至关重要的作用。

Thus, MAIT cells may be implicated in mucosal alterations of SS patients. Activation markers, inflammatory and cytotoxic cytokines were examined in 23 SS patients and compared to 23 healthy controls (HC). Tissular MAIT cells in salivary gland (SG) biopsies were also analyzed. Circulating MAIT cells were decreased in SS patients with a higher expression of CD69 and a higher CD4/CD8 ratio of MAIT cells.

。在23名SS患者中检查了激活标志物，炎症和细胞毒性细胞因子，并与23名健康对照（HC）进行了比较。还分析了唾液腺（SG）活组织检查中的组织MAIT细胞。在CD69表达较高且MAIT细胞CD4/CD8比率较高的SS患者中，循环MAIT细胞减少。

MAIT cells showed a higher production of IFNγ, TNFα and GzB in SS compare to HC. Tissular MAIT cells were present within inflamed SG of SS patients, while they were absent in SG of HC. Overall, circulating MAIT cells are decreased in the peripheral blood of SS albeit producing higher amounts of IFNγ, TNFα, and GzB.

与HC相比，MAIT细胞在SS中显示出更高的IFNγ，TNFα和GzB产生。SS患者发炎的SG中存在组织MAIT细胞，而HC的SG中不存在组织MAIT细胞。总体而言，SS外周血中的循环MAIT细胞减少，尽管产生了更高量的IFNγ，TNFα和GzB。

Tissular MAIT cells are detected in salivary glands from SS with a proinflammatory tissular cytokine environment. MAIT cells with abnormal phenotype, functions and tissular homeostasis may contribute to epithelial damage in SS..

在具有促炎性组织细胞因子环境的SS的唾液腺中检测到组织MAIT细胞。具有异常表型，功能和组织稳态的MAIT细胞可能导致SS的上皮损伤。。

IntroductionSjogren’s syndrome (SS) is a rare autoimmune disease characterized by sicca features (dryness of the eyes and mouth), resulting from chronic inflammatory infiltrates into the salivary and lacrimal glands. The current SS diagnosis criteria include the presence of anti-SSA (Ro) antibodies or focal inflammatory infiltrates (≥ 50 mononuclear cells within 4 mm2) in labial salivary glands (LSG) of patients1.

。目前的SS诊断标准包括患者唇唾液腺（LSG）中存在抗SSA（Ro）抗体或局灶性炎症浸润（4 mm2内≥50个单核细胞）1。

Higher focus score and the presence of germinal center-like structures in LSG of patients with SS have been correlated with severe disease2.Mucosal associated invariant T (MAIT) cells contribute to antibacterial and antiviral immunity, and inflammatory and autoimmune diseases, with important role in tissue homeostasis and repair3,4,5.

SS患者LSG中较高的焦点评分和生发中心样结构的存在与严重疾病相关2。粘膜相关不变T（MAIT）细胞有助于抗菌和抗病毒免疫，炎症和自身免疫性疾病，在组织稳态和修复中起重要作用3,4,5。

MAIT cells are an important subset of innate-like T lymphocytes with a restricted T cell receptor (TCR) usage, functionally related to NKT cells and γδT cells, and at the interface of the innate and adaptive response6,7. MAIT cells are predominantly localized in the mucosal tissue of organs such as the lung and the intestine, albeit they are also detected in blood (1–10% of T-cells).

MAIT细胞是先天性T淋巴细胞的重要子集，具有受限的T细胞受体（TCR）使用，与NKT细胞和γδT细胞功能相关，并且处于先天性和适应性反应的界面6,7。MAIT细胞主要位于肺和肠等器官的粘膜组织中，尽管它们也在血液中检测到（占T细胞的1-10%）。

Alteration in their proportion and function are associated with various infections, inflammation, and autoimmune diseases8. MAIT cells can be identified by flow cytometry as CD3+ TCR Vα7.2+ CD161high cells3. In the peripheral blood, they display high level of chemokine receptors (i.e. CCR6, CXCR6, CXCR4, CCR5) involved in tissue trafficking, and high level of receptor for cytokines such as IL-18, IL-12 and IL-23.

它们的比例和功能的改变与各种感染，炎症和自身免疫性疾病有关8。MAIT细胞可以通过流式细胞术鉴定为CD3+TCR Vα7.2+CD161high细胞3。在外周血中，它们显示出参与组织运输的高水平趋化因子受体（即CCR6，CXCR6，CXCR4，CCR5），以及IL-18，IL-12和IL-23等细胞因子的高水平受体。

MAIT cells can be activated through two pathways, namely a TCR-dependent pathway involving MR1+ antigen-presenting cells, and a TCR-independent pathway mediated by IL-12 and IL-18. Upon activation, MAIT cells rapidly produce inflammatory cyt.

MAIT细胞可以通过两种途径被激活，即涉及MR1+抗原呈递细胞的TCR依赖性途径和由IL-12和IL-18介导的TCR非依赖性途径。激活后，MAIT细胞迅速产生炎性细胞。

Data availability

数据可用性

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

本研究中使用和/或分析的数据集可根据合理要求从通讯作者处获得。

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Single-cell diversity and functional plasticity of human MAIT cells. Nat Immunol. 24(9), 1409–1410. https://doi.org/10.1038/s41590-023-01600-3 (2023).Download referencesAcknowledgementsJeanne Chauffier was supported by grant from Société Nationale Française de Médecine Interne and grant from Groupe Pasteur Mutualité (Villa M).

人类MAIT细胞的单细胞多样性和功能可塑性。Nat免疫。24（9），1409-1410。https://doi.org/10.1038/s41590-023-01600-3（2023年）。下载参考文献致谢Jeanne Chauffier得到了法国国家银行（SociétéNationale Française de Médecine Interne）的资助和巴斯德互助集团（Groupe Pasteur Mutualité）（Villa M）的资助。

Aïcha Kante was supported by grant from Société Nationale Française de Médecine Interne.Author informationAuthors and AffiliationsDepartment of Internal Medicine, Hôpital Lariboisière, Université Paris Cité, 2 Rue Ambroise Paré, 75010, Paris, FranceJeanne Chauffier, Aïcha Kante, Xavier Cabrol, Elisa Aldersons, Stéphane Mouly, Karine Champion, Blanca Amador-Borrero, Ruxandra Burlacu, William Bigot, Damien Sène & Cloé ComarmondINSERM UMR 976, Université Paris Cité, Institut de Recherche Saint-Louis (IRSL), 75010, Paris, FranceJeanne Chauffier, Henri Berger de Gallardo, Mathieu F.

Aïcha Kante得到了法国国家内科学会的资助。作者信息作者和附属机构内科学系，Hôpital Lariboisière，巴黎城市大学，2 rue Ambroise Paré，75010，巴黎，FranceJeanne Chauffier，Aïcha Kante，Xavier Cabrol，Elisa Aldersons，Stéphane Mouly，Karine Champion，Blanca Amador Borrero，Ruxandra Burlacu，William Bigot，Damien Sêne&CloéComarmondinserm UMR 976，巴黎城市大学圣路易斯研究所（IRSL），75010亨利·伯杰·德·加拉多，马蒂厄·F。

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PubMed Google ScholarContributionsJ.C., D.S. and C.C. developed the research concept; J.C and H.B. performed the experiments; MF.C., R.K., H.A., D.S. and C.C. validated results; MF.C., M.L., H.A., R.K., A.S., M.C., A.C., S.C. provided reagents and technical support; J.C. and C.C.

PubMed谷歌学术贡献。C、 ，D.S.和C.C.开发了研究概念；J、 C和H.B.进行了实验；MF.C.，R.K.，H.A.，D.S.和C.C.验证结果；MF.C.，M.L.，H.A.，R.K.，A.S.，M.C.，A.C.，S.C.提供试剂和技术支持；J、 C.和C.C。

performed statistical analyses; A.K., X.C., E.A., R.B., K.C., B.A., W.B., S.M., D.S. and C.C. recruited patients; J.C., H.B., A.S. and A.C. performed sample processing; J.C., D.S. and C.C. wrote the main manuscript; J.C., MF.C., S.M., D.S. and C.C. reviewed and edited the main manuscript. All authors have read and agreed to the published version of the manuscript.Corresponding authorCorrespondence to.

进行统计分析；A、 K.，X.C.，E.A.，R.B.，K.C.，B.A.，W.B.，S.M.，D.S.和C.C.招募的患者；J、 C.，H.B.，A.S.和A.C.进行了样品处理；J、 C.，D.S.和C.C.撰写了主要手稿；J、 C.，MF.C.，S.M.，D.S.和C.C.审查并编辑了主要手稿。所有作者均已阅读并同意稿件的发布版本。。

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Reprints and permissionsAbout this articleCite this articleChauffier, J., Berger de Gallardo, H., Chevalier, M.F. et al. Role of mucosal-associated invariant T cells dynamics in pathogenesis of Sjögren syndrome.

转载和许可本文引用本文Chauffer，J.，Berger de Gallardo，H.，Chevalier，M.F。等人。粘膜相关不变T细胞动力学在干燥综合征发病机制中的作用。

Sci Rep 14, 17256 (2024). https://doi.org/10.1038/s41598-024-67901-1Download citationReceived: 19 January 2024Accepted: 17 July 2024Published: 27 July 2024DOI: https://doi.org/10.1038/s41598-024-67901-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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Mechanisms of diseasePathogenesisRheumatology

疾病发病机制风湿病学

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