The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

• Authors: Dahae Lee, Seoul National University; Hyejung Jo, Seoul National University; Cheolhyeon Go, Seoul National University; Yoojin Jang, Seoul National University; Naghyung Chu, Emory University; Suhyun Bae, Seoul National University; Dongmin Kang, Boston University; Yejin Kim, Seoul National University; Jae Seung Kang, Seoul National University
• Journal Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: Volume 23, Number 2
• Publisher: MDPI | 2022-01-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/ijms23020757
• Subjects: Health Sciences, Immunology; Biology, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry; IL-22; IL-22R alpha; inflammation; BV2; HT22; T-CELLS; DISEASE; EXPRESSION; SYSTEM; MEMORY

Abstract

Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rβ subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.