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Article

The Interplay of Type 1, Type 2, and Type 3 Lymphocytes and Cytokines in Atopic Dermatitis

by
Keiichi Yamanaka
1,*,
Yui Kono
1,
Shohei Iida
1,
Takehisa Nakanishi
1,
Mai Nishimura
1,
Yoshiaki Matsushima
1,
Makoto Kondo
1,
Koji Habe
1 and
Yasutomo Imai
1,2
1
Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan
2
Imai Adult and Pediatric Dermatology Clinic, 5-1-1 Ebie, Fukushima, Osaka 553-0001, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(4), 3310; https://doi.org/10.3390/ijms24043310
Submission received: 11 January 2023 / Revised: 31 January 2023 / Accepted: 1 February 2023 / Published: 7 February 2023
(This article belongs to the Special Issue Molecular Advances in Skin Diseases 2.0)
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Abstract

Atopic dermatitis (AD) is classified as a type 2 disease owing to the majority of type 2 lymphocytes that constitute the skin-infiltrating leukocytes. However, all of the type 1–3 lymphocytes intermingle in inflamed skin lesions. Here, using an AD mouse model where caspase-1 was specifically amplified under keratin-14 induction, we analyzed the sequential changes in type 1–3 inflammatory cytokines in lymphocytes purified from the cervical lymph nodes. Cells were cultured and stained for CD4, CD8, and γδTCR, followed by intracellular cytokines. Cytokine production in innate lymphocyte cells (ILCs) and the protein expression of type 2 cytokine IL-17E (IL-25) were investigated. We observed that, as inflammation progresses, the cytokine-producing T cells increased and abundant IL-13 but low levels of IL-4 are produced in CD4-positive T cells and ILCs. TNF-α and IFN-γ levels increased continuously. The total number of T cells and ILCs peaked at 4 months and decreased in the chronic phase. In addition, IL-25 may be simultaneously produced by IL-17F-producing cells. IL-25-producing cells increased in a time-dependent manner during the chronic phase and may work specifically for the prolongation of type 2 inflammation. Altogether, these findings suggest that inhibition of IL-25 may be a potential target in the treatment of inflammation.
Keywords: atopic dermatitis; inflammatory skin mouse model; cytokine; type 2 inflammation; interleukin-17E; interleukin-25 atopic dermatitis; inflammatory skin mouse model; cytokine; type 2 inflammation; interleukin-17E; interleukin-25

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MDPI and ACS Style

Yamanaka, K.; Kono, Y.; Iida, S.; Nakanishi, T.; Nishimura, M.; Matsushima, Y.; Kondo, M.; Habe, K.; Imai, Y. The Interplay of Type 1, Type 2, and Type 3 Lymphocytes and Cytokines in Atopic Dermatitis. Int. J. Mol. Sci. 2023, 24, 3310. https://doi.org/10.3390/ijms24043310

AMA Style

Yamanaka K, Kono Y, Iida S, Nakanishi T, Nishimura M, Matsushima Y, Kondo M, Habe K, Imai Y. The Interplay of Type 1, Type 2, and Type 3 Lymphocytes and Cytokines in Atopic Dermatitis. International Journal of Molecular Sciences. 2023; 24(4):3310. https://doi.org/10.3390/ijms24043310

Chicago/Turabian Style

Yamanaka, Keiichi, Yui Kono, Shohei Iida, Takehisa Nakanishi, Mai Nishimura, Yoshiaki Matsushima, Makoto Kondo, Koji Habe, and Yasutomo Imai. 2023. "The Interplay of Type 1, Type 2, and Type 3 Lymphocytes and Cytokines in Atopic Dermatitis" International Journal of Molecular Sciences 24, no. 4: 3310. https://doi.org/10.3390/ijms24043310

APA Style

Yamanaka, K., Kono, Y., Iida, S., Nakanishi, T., Nishimura, M., Matsushima, Y., Kondo, M., Habe, K., & Imai, Y. (2023). The Interplay of Type 1, Type 2, and Type 3 Lymphocytes and Cytokines in Atopic Dermatitis. International Journal of Molecular Sciences, 24(4), 3310. https://doi.org/10.3390/ijms24043310

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