Characteristic Pattern of IL-17RA, IL-17RB, and IL-17RC in Monocytes/Macrophages and Mast Cells From Patients With Bullous Pemphigoid

• Published in: Frontiers in immunology Vol. 10; p. 2107
• Main Authors: Nesmond, Stéphane, Muller, Céline, Le Naour, Richard, Viguier, Manuelle, Bernard, Philippe, Antonicelli, Frank, Le Jan, Sébastien
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 11.09.2019; Frontiers Media S.A
• Subjects: autoimmunity; bullous pemphigoid; Dermatology; Human health and pathology; IL-17 isoforms; IL-17 receptors; Immunology; inflammation; Life Sciences; IL-17 receptors; bullous pemphigoid; autoimmunity; inflammation; IL-17 isoforms
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02107

Inflammation is largely implicated in bullous pemphigoid (BP), the most frequent skin auto-immune blistering disease. IL-17, essentially IL-17A/F, has been involved in blister formation through regulation of protease production, and its specific serum profile within BP was related to disease outcome. However, relationships between IL-17 family ligands and receptors are quite complex with six different IL-17 isoforms, and five different receptors. We here aimed at clarifying the contribution of the IL-17 axis in BP by characterizing not only the expression of IL-17 receptor (IL-17R) members within immune cells isolated from BP patients (PMNs, = 9; T-lymphocytes, = 10; and monocytes, = 10) but also the expression of IL-17 isoforms in sera ( = 83), and blister fluid ( = 31) of BP patients. We showed that at diagnosis, IL-17RA and IL-17RC expression were significantly increased in monocytes isolated from BP patients as compared to those from control subjects ( = 0.006 and = 0.016, respectively). Notably, both IL-17RA and IL-17RC mRNA expression remained elevated in BP monocytes at time of relapse. We further demonstrated a significant increase of all IL-17 isoforms tested in BP blister fluid compared with BP serum (IL-17A, < 0.0001; IL-17A/F, < 0.0001; IL-17B, = 0.0023; IL-17C, = 0.0022; IL-17E, < 0.0001). Among all, IL-17B was the only cytokine for which a significant decreased concentration within blister fluid was observed in BP patients with severe disease compared to patients with moderate disease ( = 0.012). We further evidenced a significant negative correlation between IL-17B levels and blister/erosion BPDAI subscore ( = -0.52, = 0.003). We finally identified mast cells as a potential target of IL-17B in lesional skin of BP patients. In conclusion, we showed here that IL-17RA and IL-17RC expression in monocyte was associated with disease activity and evidenced a negative correlation between BP disease activity and IL-17B, whose effects could be mediated by IL-17RB expressed by mast cell in BP lesional skin.