A possible interaction between periostin and CD163⁺ skin‐resident macrophages in pemphigus vulgaris and bullous pemphigoid

Abstract

Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are autoimmune blistering diseases, and substantial numbers of CD163 tissue-associated macrophages (TAMs) are detected in both diseases. PV and BP possess different subsets of helper T cells, suggesting that the cytokine profiles of PV and BP might be different. The purpose of this study was to investigate the microenvironment of lesional skin and serum of PV and BP patients, focusing on the immunomodulatory factors related to TAMs, such as periostin (POSTN), chemokines, cytokines and matrix metalloproteinases (MMPs). We first performed immunohistological staining of POSTN in PV and BP lesions. POSTN was prominent in the superficial dermis in both PV and BP lesions. Next, to validate the activation of CD163 TAMs in PV and BP patients, we examined the serum levels of soluble (s)CD163. The serum sCD163 levels in PV and BP patients are significantly higher than in healthy controls. To further elucidate the molecular mechanisms of the effects of POSTN on CD163 TAMs in PV and BP, we examined chemokines, MMPs and cytokines selected by DNA microarray database. The serum CXCL5 levels from PV patients are significantly higher than those in BP patients and healthy controls. The IL-36γ expression on infiltrating macrophages was prominent only in the lesional skin of PV, while the MMP12 deposition was detected in both PV and BP lesions. Our results shed light on the novel pathogenesis of PV through CD163 TAMs.

Minocycline decreases Th2 chemokines from M2 macrophages: Possible mechanisms for the suppression of bullous pemphigoid by traditional bullous disease drugs

“…As indicated in Figures and and a previous report, M2 macrophages produce CCL18 and CCL22 in the lesional skin of BP, leading to a significant increase in serum CCL18 and CCL22. Since NAA, minocycline, dexamethasone and cyclosporine have been clinically used for the treatment of BP, we hypothesized that these drugs might affect the production of chemokines from CD163 + M2 macrophages.…”

“…As previous reports suggested, serum CXCL10 is significantly increased in BP patients. In addition, as we previously reported, CD163 + M2 macrophages are stimulated by periostin (POSTN) and IL‐4, leading to activation and the production of a series of chemokines, including Th2‐related chemokines (CCL17, CCL18, CCL22, CCL24 and CCL26) . Guenter et al suggested that the serum levels of CCL18 correlate with the disease severity of BP.…”

“…Guenter et al suggested that the serum levels of CCL18 correlate with the disease severity of BP. In addition, the serum levels of soluble CD163 (sCD163) are significantly increased in BP patients as compared to healthy donors, suggesting that CD163 + macrophages are activated in patients with BP, whereas there is no significant difference in serum CXCL5 or proinflammatory chemokines in BP compared to healthy donors . Given these reports, we first examined the serum levels of CCL17, CCL22 and CXCL10, all of which are increased in CD163 + M2 macrophages by stimulation with POSTN and IL‐4 in patients with BP as well as healthy donors according to ELISA.…”

Pruritus in ordinary scabies: IL‐31 from macrophages induced by overexpression of thymic stromal lymphopoietin and periostin

“…IFN‐γ‐treated M1 macrophages failed to generate IL‐31. A prior report with human monocytes/macrophages also showed that periostin induced IL‐31 production . These data suggested that TSLP and periostin expressed in human scabies lesions were essentially involved in IL‐31 generation from M2 macrophages.…”

Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

“…Although it was not possible to detect CXCL9, CXCL10 and CXCL11 in the present system, the antitumor effects of these chemokines are still controversial. [13,[30][31][32][33][34] Th1 chemokines recruit effector T cells in the tumor site, [31,32] but their role in tumor progression differs between tumor types. [32] The expression of CXCL10 recruits the effector and cytotoxic T cells in mice and humans, [13,19] but CXCL10 derived from myeloid cells is also reported to be a poor prognostic marker for melanoma patients.…”