Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes
(1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using...
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2025-06-01
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| author | Ayaka Ichikawa Mai Nishimura Masako Ichishi Yasutomo Imai Yoshiaki Matsushima Yoichiro Iwakura Masatoshi Watanabe Kiyofumi Yamanishi Keiichi Yamanaka |
| author_facet | Ayaka Ichikawa Mai Nishimura Masako Ichishi Yasutomo Imai Yoshiaki Matsushima Yoichiro Iwakura Masatoshi Watanabe Kiyofumi Yamanishi Keiichi Yamanaka |
| author_sort | Ayaka Ichikawa |
| collection | DOAJ |
| description | (1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using wild-type, keratin 14-specific IL-33 transgenic, IL-18 transgenic, caspase-1 transgenic, and caspase-1 transgenic mice with IL-17AF deletion, reflecting diverse aspects of human skin inflammation. IL-36α was administered subcutaneously in five doses on alternate days across the five strains to examine cellular infiltration patterns and cytokine expression levels. (3) Results: The skin phenotype was exacerbated, accompanied by worsening edema and skin thickness in all mouse groups upon IL-36α administration. An increase in infiltrating cells was observed among innate immune cells, while lymphocyte counts, including T cells and innate lymphoid cells, did not rise. Additionally, anti-inflammatory cytokines were induced simultaneously with inflammatory cytokines and downstream cytokines of IL-36α as well. Infiltrating lymphocytes in the skin displayed a distinct Type 2 cytokine-dominant profile for innate lymphoid cells and a Type 3 cytokine-dominant profile for T helper cells and γδ T cells, contrasting with the Type 1-dominant cell profile in draining lymph nodes. Type 1, Type 2, and Type 3 cytokine dominance patterns were not affected by the administration of IL-36α. (4) Conclusions: IL-36α triggers inflammatory responses in atopic dermatitis by activating innate immunity. The infiltrating lymphocytes in the skin have different cytokine production profiles between innate lymphoid cells and T cells, as well as different patterns of cytokine production in their draining lymph nodes. |
| format | Article |
| id | doaj-art-4f459a7f02ae4d6186c569eb5ea9bd36 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-4f459a7f02ae4d6186c569eb5ea9bd362025-08-20T03:27:29ZengMDPI AGBiomolecules2218-273X2025-06-0115681710.3390/biom15060817Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph NodesAyaka Ichikawa0Mai Nishimura1Masako Ichishi2Yasutomo Imai3Yoshiaki Matsushima4Yoichiro Iwakura5Masatoshi Watanabe6Kiyofumi Yamanishi7Keiichi Yamanaka8Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Biomedical Science, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo 113-8657, JapanDepartment of Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, JapanDepartment of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, Japan(1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using wild-type, keratin 14-specific IL-33 transgenic, IL-18 transgenic, caspase-1 transgenic, and caspase-1 transgenic mice with IL-17AF deletion, reflecting diverse aspects of human skin inflammation. IL-36α was administered subcutaneously in five doses on alternate days across the five strains to examine cellular infiltration patterns and cytokine expression levels. (3) Results: The skin phenotype was exacerbated, accompanied by worsening edema and skin thickness in all mouse groups upon IL-36α administration. An increase in infiltrating cells was observed among innate immune cells, while lymphocyte counts, including T cells and innate lymphoid cells, did not rise. Additionally, anti-inflammatory cytokines were induced simultaneously with inflammatory cytokines and downstream cytokines of IL-36α as well. Infiltrating lymphocytes in the skin displayed a distinct Type 2 cytokine-dominant profile for innate lymphoid cells and a Type 3 cytokine-dominant profile for T helper cells and γδ T cells, contrasting with the Type 1-dominant cell profile in draining lymph nodes. Type 1, Type 2, and Type 3 cytokine dominance patterns were not affected by the administration of IL-36α. (4) Conclusions: IL-36α triggers inflammatory responses in atopic dermatitis by activating innate immunity. The infiltrating lymphocytes in the skin have different cytokine production profiles between innate lymphoid cells and T cells, as well as different patterns of cytokine production in their draining lymph nodes.https://www.mdpi.com/2218-273X/15/6/817alarminatopic dermatitisinterleukin-36αinflammationpsoriasis |
| spellingShingle | Ayaka Ichikawa Mai Nishimura Masako Ichishi Yasutomo Imai Yoshiaki Matsushima Yoichiro Iwakura Masatoshi Watanabe Kiyofumi Yamanishi Keiichi Yamanaka Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes Biomolecules alarmin atopic dermatitis interleukin-36α inflammation psoriasis |
| title | Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes |
| title_full | Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes |
| title_fullStr | Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes |
| title_full_unstemmed | Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes |
| title_short | Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes |
| title_sort | enhanced innate immunity mediated by il 36α in atopic dermatitis and differences in cytokine profiles of lymphocytes in the skin and draining lymph nodes |
| topic | alarmin atopic dermatitis interleukin-36α inflammation psoriasis |
| url | https://www.mdpi.com/2218-273X/15/6/817 |
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