2020.05.01 Journal club

IL-37 is protective in allergic contact dermatitis through mast cell inhibition 

Weihua Lia, Fengmin Dingb, Yi Zhaia, Wenting Taob, Jing Bic, Hong Fanc, Nina Yind,

Zhigang Wangc,⁎

a Department of Cardiology, Affiliated Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China b School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China
c Department of Pathogen Biology, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China
d Department of Anatomy, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China

ABSTRACT

Allergic contact dermatitis (ACD), characterized predominantly by erythema, vesiculation, and pruritus, is a T cell-mediated skin inflammatory condition. Among immune cells involved in ACD, mast cells (MCs) play an essential role in its pathogenesis. As an inhibitor of proinflammatory IL-1 family members, interleukin 37 (IL-37) has been shown to ameliorate inflammatory responses in various allergic diseases. In this study, we assessed the immunomodulatory effect of IL-37 on allergic inflammation using a 2,4-dinitrofluorobenzene (DNFB)-induced ACD rat model and isolated rat peritoneal mast cells (RPMCs). Systematic application of IL-37 significantly relieved ear swelling, reduced inflammatory cell infiltration, decreased inflammatory cytokine production (TNF- α, IL-1β, IFN-γ, and IL-13), inhibited MC recruitment, lowered IgE levels, and reduced IL-33 production in the local ear tissues with DNFB challenge. Additionally, RPMCs isolated from ACD rats with IL-37 intervention showed downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation, and reduction of β-hexosaminidase and histamine release under DNP-IgE/HSA treatment. Moreover, IL-37 treatment also significantly restrained NF-κB activation and P38 phosphorylation in ACD RPMCs. SIS3, a specific Smad3 in- hibitor, abolished the suppressive effects of IL-37 on MC-mediated allergic inflammation, suggesting the parti- cipation of Smad3 in the anti-ACD effect of IL-37. These findings indicated that IL-37 protects against IL-33- regulated MC inflammatory responses via inhibition of NF-κB and P38 MAPK activation accompanying the regulation of Smad3 in rats with ACD.