Suppression of IL-23-mediated psoriasis-like inflammation by regulatory B cells

• Published in: Scientific reports Vol. 11; no. 1; p. 2106
• Main Authors: Mizumaki, Kie, Horii, Motoki, Kano, Miyu, Komuro, Akito, Matsushita, Takashi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 22.01.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adoptive transfer; Animals; B-Lymphocytes, Regulatory - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation - drug effects; Cell Differentiation - immunology; Ear; Female; Helper cells; Immunoregulation; Inflammation; Inflammation - immunology; Inflammation - pathology; Injections, Intradermal; Interleukin 10; Interleukin 23; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukin-23 - administration & dosage; Interleukin-23 - genetics; Interleukin-23 - immunology; Lymph nodes; Lymphocytes B; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Psoriasis; Psoriasis - immunology; Psoriasis - pathology; PTEN Phosphohydrolase - deficiency; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - immunology; PTEN protein; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Skin diseases; Spleen; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tensin; Th17 Cells - cytology; Th17 Cells - drug effects; Th17 Cells - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-81588-8

Psoriasis is an inflammatory cutaneous disease mediated by T-cell dependent immune responses; however, B cells are also considered to play an important role its development. Regulatory B cells (Bregs) regulate immune responses negatively through interleukin-10 (IL-10) production. This study aimed to investigate the role of Bregs in IL-23-mediated psoriasis-like inflammation in mice. Psoriasis-like inflammation was induced in B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice, in which Bregs were significantly expanded, and in their controls, by intradermal injection of 20 μL phosphate-buffered saline (PBS) containing 0.5 μg rmIL-23 into one ear, every other day for 16 days. IL-23-mediated psoriasis-like inflammation was suppressed in B cell-specific PTEN-deficient mice along with decreased ear thickness and epidermal thickness on day 15. Moreover, adoptive transfer of B1 B cells suppressed IL-23-mediated psoriasis-like inflammation. rmIL-23-injected B cell-specific PTEN-deficient mice showed expanded regulatory T cells (Tregs) in the spleen and draining lymph nodes along with increased Bregs. Further, T helper (Th) 17 differentiation in the rmIL-23-injected ear was suppressed in B cell-specific PTEN-deficient mice. Overall, these results indicate that increased Bregs suppress IL-23-mediated psoriasis-like inflammation through Treg expansion and inhibition of Th17 differentiation. Thus, targeting Bregs may be a feasible treatment strategy for psoriasis.