CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjögren's Syndrome.
CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjögren's Syndrome.
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DOI：
10.3389/fimmu.2018.02594
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发表时间：
2018
影响因子：
7.3
通讯作者：
Ishimaru N
中科院分区：
文献类型：
--
作者：
Ushio A;Arakaki R;Otsuka K;Yamada A;Tsunematsu T;Kudo Y;Aota K;Azuma M;Ishimaru N
巨噬细胞(MΦ，S)是免疫反应的重要调节者，是连接先天免疫和后天免疫的纽带。组织内MΦS参与自身免疫性疾病发病的确切机制尚不清楚。在这里，我们使用干燥综合征(SS)的小鼠模型，研究了组织常驻MΦS在自身免疫的发生和发展中的作用。在SS模型靶组织中观察到CD11bHigh和CD11bllow常驻MΦS两个独特的群体。趋化因子基因表达的综合分析表明，CD11bHigh MΦS有效地产生了CCL22，CCL22通过增加CCL22受体CCR4上调了SS模型小鼠T细胞表面CCL22的迁移活性。此外，CCL22还能促进SS模型小鼠T细胞产生干扰素-γ，提示CCL22可能损害SS模型靶器官的局部免疫耐受。此外，给予抗CCL22抗体可抑制SS模型中的自身免疫损伤。组织病理学检查发现SS患者的小涎腺组织中有大量产生CCL22的MΦS。产生CCL22的组织常驻MΦS可能通过增强SS模型中的T细胞反应来控制自身免疫性病变。这些结果提示，特异性趋化因子及其受体可能成为SS的新的治疗或诊断靶点。
Macrophages (MΦs) are critical regulators of immune response and serve as a link between innate and acquired immunity. The precise mechanism of involvement of tissue-resident MΦs in the pathogenesis of autoimmune diseases is not clear. Here, using a murine model for Sjögren's syndrome (SS), we investigated the role of tissue-resident MΦs in the onset and development of autoimmunity. Two unique populations of CD11bhigh and CD11blow resident MΦs were observed in the target tissue of the SS model. Comprehensive gene expression analysis of chemokines revealed effective production of CCL22 by the CD11bhigh MΦs. CCL22 upregulated the migratory activity of CD4+ T cells by increasing CCR4, a receptor of CCL22, on T cells in the SS model. In addition, CCL22 enhanced IFN-γ production of T cells of the SS model, thereby suggesting that CCL22 may impair the local immune tolerance in the target organ of the SS model. Moreover, administration of anti-CCL22 antibody suppressed autoimmune lesions in the SS model. Finally, histopathological analysis revealed numerous CCL22-producing MΦs in the minor salivary gland tissue specimens of the SS patients. CCL22-producing tissue-resident MΦs may control autoimmune lesions by enhancing T cell response in the SS model. These results suggest that specific chemokines and their receptors may serve as novel therapeutic or diagnostic targets for SS.
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影响因子：
7.3
作者：
Greter M;Lelios I;Croxford AL
通讯作者：
Croxford AL
影响因子：
--
作者：
Greenwell-Wild, Teresa;Moutsopoulos, Niki M.;Gliozzi, Maria;Kapsogeorgou, Efstathia;Rangel, Zoila;Munson, Peter J.;Moutsopoulos, Haralampos M.;Wahl, Sharon M.
通讯作者：
Wahl, Sharon M.
影响因子：
--
作者：
FOX, RI;ROBINSON, CA;HOWELL, FV
通讯作者：
HOWELL, FV
DOI：
10.1016/0030-4220(74)90417-4
发表时间：
1974-01-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
--
作者：
GREENSPAN, JS;DANIELS, TE;SYLVESTER, RA
通讯作者：
SYLVESTER, RA
影响因子：
3.8
作者：
Flytlie, Helene Aarslev;Hvid, Malene;Deleuran, Bent
通讯作者：
Deleuran, Bent