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

Abstract

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, n = 9; T-lymphocytes, n = 10; and monocytes, n = 10) but also the expression of IL-17 isoforms in sera (n = 83), and blister fluid (n = 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 (p = 0.006 and p = 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, p < 0.0001; IL-17A/F, p < 0.0001; IL-17B, p = 0.0023; IL-17C, p = 0.0022; IL-17E, p < 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 (p = 0.012). We further evidenced a significant negative correlation between IL-17B levels and blister/erosion BPDAI subscore (r = −0.52, p = 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 in situ 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.

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

“…IL-17A plays an essential role in inflammation, metabolism, and bone/joint damage (8,10,15,(60)(61)(62). The IL-17 levels and Th17 cell frequencies are high in the skin, synovial fluid, and synovium tissue of the patients with psoriatic arthritis (PsA) (18,(63)(64)(65).…”

“…The cytokines, interleukin-23 (IL-23) and IL-17, have been confirmed to markedly affect chronic inflammation (10,(13)(14)(15)(16). In addition, the discovery of the IL-23/IL-17 pathway has contributed to a clearer understanding of the underlying mechanism of inflammatory diseases.…”

Study of immune response of immune mediator interleukin (17 and 23) against dermatophytes infection

“…IL-17R-deficient mice were inoculated intravenously with Candida albicans and displayed lower survival and higher kidney fungal burden as compared to WT counterparts, respectively, in 2004, when the role of the IL-17 axis in antifungal host defense was first shown (Fabio SY, et al, 2021). However, the preponderance of evidence supports the idea that IL-17 is protective in systemic candidemia, notwithstanding a disagreement in one study (Nesmond S, et al, 2019). (Fabio SY, et al, 2021).…”

Interleukin-17A Interweaves the Skeletal and Immune Systems

“…IL-17A interacts with its receptors to activate downstream regulators and trigger cellular responses. Receptors for IL-17A are ubiquitously expressed on the cellular surface including synoviocytes, chondrocytes, fibroblasts, monocytes/macrophages, mast cells ( 20 , 21 ). Bone cells including osteoclasts and osteoblasts also express IL-17RA ( 22 ).…”