MAPK Phosphatase-1 Deficiency Exacerbates the Severity of Imiquimod-Induced Psoriasiform Skin Disease

• Published in: Frontiers in immunology Vol. 9; p. 569
• Main Authors: Zhao, Weiheng, Xiao, Shuxiu, Li, Hongjin, Zheng, Tingting, Huang, Jian, Hu, Ran, Zhang, Baohua, Liu, Xinguang, Huang, Gonghua
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.03.2018
• Subjects: Immunology; keratinocyte; macrophage; mitogen-activated protein kinase; phosphatase MAPK phosphatase-1; psoriasis; mitogen-activated protein kinase; macrophage; keratinocyte; psoriasis; phosphatase MAPK phosphatase-1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00569

Persistent activation of mitogen-activated protein kinase (MAPK) is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1) is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ)-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1 ) mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines. MKP-1 acted on both hematopoietic and non-hematopoietic cells to regulate psoriasis pathogenesis. MKP-1 deficiency in macrophages led to enhanced p38 activation and higher expression of interleukin (IL)-1β, CXCL2, and S100a8 upon R848 stimulation. Moreover, MKP-1 deficiency in the non-hematopoietic compartments led to an enhanced IL-22 receptor signaling and higher expression of CXCL1 and CXCL2 upon IMQ treatment. Collectively, our data suggest a critical role for MKP-1 in the regulation of skin inflammation.