Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata

Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However...

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Main Authors: Reiko Kageyama, Taisuke Ito, Shiho Hanai, Naomi Morishita, Shinsuke Nakazawa, Toshiharu Fujiyama, Tetsuya Honda, Yoshiki Tokura
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/5/2618
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author Reiko Kageyama
Taisuke Ito
Shiho Hanai
Naomi Morishita
Shinsuke Nakazawa
Toshiharu Fujiyama
Tetsuya Honda
Yoshiki Tokura
author_facet Reiko Kageyama
Taisuke Ito
Shiho Hanai
Naomi Morishita
Shinsuke Nakazawa
Toshiharu Fujiyama
Tetsuya Honda
Yoshiki Tokura
author_sort Reiko Kageyama
collection DOAJ
description Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4<sup>+</sup>IL-4<sup>+</sup> cells and CD4<sup>+</sup>IFN-γ<sup>+</sup> cells to CD4<sup>+</sup>IL-13<sup>+</sup> cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8<sup>+</sup>IFN-γ<sup>+</sup> cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4<sup>+</sup> cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3<sup>+</sup> cells had no remarkable change while the number of CCR4<sup>+</sup> cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.
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spelling doaj.art-e2b7ab312b1643819c7ba537a6ef12342023-12-03T12:38:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225261810.3390/ijms22052618Immunological Properties of Atopic Dermatitis-Associated Alopecia AreataReiko Kageyama0Taisuke Ito1Shiho Hanai2Naomi Morishita3Shinsuke Nakazawa4Toshiharu Fujiyama5Tetsuya Honda6Yoshiki Tokura7Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Dermatology, Seirei Hamamatsu General Hospital, Hamamatsu 431-3192, JapanDepartment of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanAlopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4<sup>+</sup>IL-4<sup>+</sup> cells and CD4<sup>+</sup>IFN-γ<sup>+</sup> cells to CD4<sup>+</sup>IL-13<sup>+</sup> cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8<sup>+</sup>IFN-γ<sup>+</sup> cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4<sup>+</sup> cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3<sup>+</sup> cells had no remarkable change while the number of CCR4<sup>+</sup> cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.https://www.mdpi.com/1422-0067/22/5/2618alopecia areataextrinsic atopic dermatitisintrinsic atopic dermatitisIL-13IFN-γ
spellingShingle Reiko Kageyama
Taisuke Ito
Shiho Hanai
Naomi Morishita
Shinsuke Nakazawa
Toshiharu Fujiyama
Tetsuya Honda
Yoshiki Tokura
Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata
International Journal of Molecular Sciences
alopecia areata
extrinsic atopic dermatitis
intrinsic atopic dermatitis
IL-13
IFN-γ
title Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata
title_full Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata
title_fullStr Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata
title_full_unstemmed Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata
title_short Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata
title_sort immunological properties of atopic dermatitis associated alopecia areata
topic alopecia areata
extrinsic atopic dermatitis
intrinsic atopic dermatitis
IL-13
IFN-γ
url https://www.mdpi.com/1422-0067/22/5/2618
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