Eosinophil-derived galectin-10 upregulates matrix metalloproteinase expression in bullous pemphigoid blisters

• Published in: Journal of dermatological science 2023-10, Vol.112 (1), p.6-14
• Main Authors: Sato, Takahiko, Chiba, Takahito, Nakahara, Takeshi, Watanabe, Ken, Sakai, Sawako, Noguchi, Natsuko, Noto, Mai, Ueki, Shigeharu, Kono, Michihiro
• Format: Article
• Language: English
• ISSN: 1873-569X
• DOI: 10.1016/j.jdermsci.2023.07.008

BACKGROUNDBullous pemphigoid (BP) is an autoimmune bullous disease in which abundant eosinophils accumulate in the blisters. Galectin-10 abounds in the cytoplasm of eosinophils and is released as a result of eosinophil extracellular trap cell death (EETosis).OBJECTIVETo identify EETosis and the pathological roles of galectin-10 in BP.METHODSEETosis and galectin-10 in BP blisters were confirmed by immunofluorescence and transmission electron microscopy. The concentrations of galectin-10 in serum and blister fluid from BP patients were studied by ELISA. The matrix metalloproteinase (MMP) expression in BP blisters was immunohistochemically compared to that in healthy controls. As an in vitro assay, normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) were stimulated with galectin-10, followed by MMP expression measurement by real-time PCR and ELISA. The signaling pathways activated by galectin-10 were studied using Western blotting and confirmed by inhibition assays.RESULTSGalectin-10-containing eosinophil infiltration and the extracellular deposition of major basic protein were observed in BP blisters. The ultrastructural characteristics of tissue eosinophils indicated piecemeal degranulation and EETosis. In the BP patients, the concentration of galectin-10 was higher in the blister fluid than in the serum. Several types of MMPs were upregulated in BP blisters. Galectin-10 upregulated the production of MMPs through the pathways of p38 MAPK, ERK and JNK in NHEKs and NHDFs.CONCLUSIONIn the BP blisters, the eosinophils underwent EETosis and released galectin-10. Galectin-10 might contribute to BP blister formation through the production of MMPs by keratinocytes and fibroblasts.