期刊
JOURNAL OF DERMATOLOGY
卷 48, 期 3, 页码 353-359出版社
WILEY
DOI: 10.1111/1346-8138.15713
关键词
bullous pemphigoid; CXCL13; CXCR5; follicular helper T cells; LL37
类别
资金
- Japan Agency for Medical Research and Development [18lm0203062h0001]
The study indicates that CXCL13/CXCR5-mediated migration of Tfh cells plays a role in the development of BP, with CXCL13 levels positively correlated with antibody titers in BP patients. LL37 promotes the secretion of chemokines by M2 macrophages, with CXCL10 acting as a negative regulator in BP development.
CXCL13 recruits CXCR5(+) follicular helper T (Tfh) cells in inflammatory lesions to develop secondary lymphoid organs. Tfh cells activate B cells to produce antibodies during humoral immune responses. Indeed, as previous reports suggested, CXCR5(+) cell numbers were increased in the peripheral blood of bullous pemphigoid (BP) patients when compared with healthy donors, and the ratio of CXCR5(+) cells was positively correlated with the anti-BP180-NC16A titers. From the above findings, in this report, we hypothesized that a chemokine related to CXCR5(+) cells, namely CXCL13, may play a role in the development of BP. We performed immunohistochemical staining of CXCR5, CXCL13, LL37, CXCL10 and CCL20 for 10 cases of BP and 10 cases of pemphigus vulgaris (PV), and quantitatively analyzed the staining by digital microscopy. Moreover, we investigated the CXCL10 and CXCL13 production in BP and PV patients by enzyme-linked immunosorbent assay. The immunomodulatory effects of LL37 on the production of T-helper 17-related chemokines were evaluated using monocyte-derived M2 macrophages. Immunohistochemical staining and digital microscopic analysis showed that the ratios of CXCR5(+), CXCL13(+) and LL37(+) cells in the dermis were significantly higher in BP patients than in PV patients. Notably, the ratio of CXCL13(+) cells was positively correlated with the anti-BP180-NC16A titers. Moreover, the serum levels of CXCL13 were positively correlated with the anti-BP180-NC16A titers. Furthermore, CD163(+) M2 macrophages stimulated by LL37 in vitro produced CXCL10 and CCL20. In the lesional skin of BP, CD163(+) macrophages CXCL10 and CCL20 were produced. The serum levels of CXCL10 were negatively correlated with the anti-BP180-NC16A titers. The present study results indicate that the mechanism of the development of BP may involve the CXCL13/CXCR5-mediated migration of Tfh cells.
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