| First Author | Hashiguchi Y | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 1 | Pages | 167-182 |
| PubMed ID | 29794016 | Mgi Jnum | J:263315 |
| Mgi Id | MGI:6164077 | Doi | 10.4049/jimmunol.1701157 |
| Citation | Hashiguchi Y, et al. (2018) IL-36alpha from Skin-Resident Cells Plays an Important Role in the Pathogenesis of Imiquimod-Induced Psoriasiform Dermatitis by Forming a Local Autoamplification Loop. J Immunol 201(1):167-182 |
| abstractText | IL-36alpha (gene symbol Il1f6), a member of the IL-36 family, is closely associated with inflammatory diseases, including colitis and psoriasis. In this study, we found that Il1f6(-/-) mice developed milder psoriasiform dermatitis upon treatment with imiquimod, a ligand for TLR ligand 7 (TLR7) and TLR8, whereas Il1f6(-/-) mice showed similar susceptibility to dextran sodium sulfate-induced colitis to wild-type mice. These effects were observed in both cohoused and separately housed conditions, and antibiotic treatment did not cancel the resistance of Il1f6(-/-) mice to imiquimod-induced dermatitis. Bone marrow (BM) cell transfer revealed that IL-36alpha expression in skin-resident cells is important for the pathogenesis of dermatitis in these mice. Following stimulation with IL-36alpha, the expression of Il1f6 and Il1f9 (IL-36gamma), but not Il1f8 (IL-36beta), was enhanced in murine BM-derived Langerhans cells (BMLCs) and murine primary keratinocytes but not in fibroblasts from mice. Upon stimulation with agonistic ligands of TLRs and C-type lectin receptors (CLRs), Il1f6 expression was induced in BMLCs and BM-derived dendritic cells. Furthermore, IL-36alpha stimulation resulted in significantly increased gene expression of psoriasis-associated Th17-related cytokines and chemokines such as IL-1alpha, IL-1beta, IL-23, CXCL1, and CXCL2 in BMLCs and fibroblasts, and IL-1alpha, IL-1beta, IL-17C, and CXCL2 in keratinocytes. Collectively, these results suggest that TLR/CLR signaling-induced IL-36alpha plays an important role for the development of psoriasiform dermatitis by enhancing Th17-related cytokine/chemokine production in skin-resident cells via a local autoamplification loop. |
