Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells

Abstract Background Alopecia areata (AA) is an organ‐specific autoimmune disease resulting from the attack of hair follicle (HF) autoantigens through a T‐cell‐mediated mechanism. If there is a depletion of mTregs in HFs, especially around both hair bulge and hair bulb, it could be related to patchy...

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Main Authors: Ho‐Jin Kim, Jung‐Hwan Kim, Yu‐Ri Cho, Hyeok‐Jin Kwon, Jung‐Ho Yoon, Ki‐Ho Kim
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:JEADV Clinical Practice
Subjects:
Online Access:https://doi.org/10.1002/jvc2.104
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author Ho‐Jin Kim
Jung‐Hwan Kim
Yu‐Ri Cho
Hyeok‐Jin Kwon
Jung‐Ho Yoon
Ki‐Ho Kim
author_facet Ho‐Jin Kim
Jung‐Hwan Kim
Yu‐Ri Cho
Hyeok‐Jin Kwon
Jung‐Ho Yoon
Ki‐Ho Kim
author_sort Ho‐Jin Kim
collection DOAJ
description Abstract Background Alopecia areata (AA) is an organ‐specific autoimmune disease resulting from the attack of hair follicle (HF) autoantigens through a T‐cell‐mediated mechanism. If there is a depletion of mTregs in HFs, especially around both hair bulge and hair bulb, it could be related to patchy hair loss in the scalp and may affect AA pathogenesis. Objectives we investigated the possible contributory role of tissue‐resident memory T cells (TRMs) and memory regulatory T cells (mTregs), compared to cytotoxic T lymphocytes and Th17 lymphocytes, in the immunopathogenesis of chronic AA. Methods Three hundred and sixty‐seven patients with AA who had biopsies performed in Dong‐A University Hospital between January 1994 and April 2019 were retrospectively reviewed. To investigate the expression of immunoregulatory molecules, we underwent double direct immunofluorescence with paraffin sections from nine AA patients under classified according to the histopathological grading of Uno and Orecchia's classification. Results The number of lesional Foxp3+ Tregs was significantly decreased with an increase in the severity of histopathological gradings at both the hair bulge and hair bulb, in the following order: Type 1 > type 2 > type 3 AA lesions. The number of CD8+ CD69+ TRM cells at both the HF bulge and bulb was increased with the severity of histopathological grades. CD49a was not expressed in the hair bulge and bulb in any type of AA. As for the expression profile of effector T cells, interleukin (IL)‐17 was expressed in a denser pattern around the hair bulge with more severe histopathological grading, but IFN‐γ was expressed only at the hair bulge of type 1 AA. Lesional IL‐17 around the hair bulb also increased with the severity of histopathological grade. In contrast, IFN‐γ was expressed in the hair bulb only in type 1 AA. Conclusions The insidious destruction of hair bulge stem cells and hair bulb matrix stem cells, which is mediated by Th17 lymphocytes and cytotoxic T lymphocyte infiltration, results in more severe hair loss in patients with chronic AA. IL‐17 may play a more important role in the pathogenesis of chronic AA than IFN‐γ.
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spelling doaj.art-3bda4d0fab9543ada386305a2c18620b2023-06-01T15:13:20ZengWileyJEADV Clinical Practice2768-65662023-06-012222523610.1002/jvc2.104Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cellsHo‐Jin Kim0Jung‐Hwan Kim1Yu‐Ri Cho2Hyeok‐Jin Kwon3Jung‐Ho Yoon4Ki‐Ho Kim5Department of Dermatology, College of Medicine Dong‐A University Busan KoreaDepartment of Dermatology, College of Medicine Dong‐A University Busan KoreaDepartment of Dermatology, College of Medicine Dong‐A University Busan KoreaDepartment of Dermatology, College of Medicine Dong‐A University Busan KoreaDepartment of Dermatology, College of Medicine Dong‐A University Busan KoreaDepartment of Dermatology, College of Medicine Dong‐A University Busan KoreaAbstract Background Alopecia areata (AA) is an organ‐specific autoimmune disease resulting from the attack of hair follicle (HF) autoantigens through a T‐cell‐mediated mechanism. If there is a depletion of mTregs in HFs, especially around both hair bulge and hair bulb, it could be related to patchy hair loss in the scalp and may affect AA pathogenesis. Objectives we investigated the possible contributory role of tissue‐resident memory T cells (TRMs) and memory regulatory T cells (mTregs), compared to cytotoxic T lymphocytes and Th17 lymphocytes, in the immunopathogenesis of chronic AA. Methods Three hundred and sixty‐seven patients with AA who had biopsies performed in Dong‐A University Hospital between January 1994 and April 2019 were retrospectively reviewed. To investigate the expression of immunoregulatory molecules, we underwent double direct immunofluorescence with paraffin sections from nine AA patients under classified according to the histopathological grading of Uno and Orecchia's classification. Results The number of lesional Foxp3+ Tregs was significantly decreased with an increase in the severity of histopathological gradings at both the hair bulge and hair bulb, in the following order: Type 1 > type 2 > type 3 AA lesions. The number of CD8+ CD69+ TRM cells at both the HF bulge and bulb was increased with the severity of histopathological grades. CD49a was not expressed in the hair bulge and bulb in any type of AA. As for the expression profile of effector T cells, interleukin (IL)‐17 was expressed in a denser pattern around the hair bulge with more severe histopathological grading, but IFN‐γ was expressed only at the hair bulge of type 1 AA. Lesional IL‐17 around the hair bulb also increased with the severity of histopathological grade. In contrast, IFN‐γ was expressed in the hair bulb only in type 1 AA. Conclusions The insidious destruction of hair bulge stem cells and hair bulb matrix stem cells, which is mediated by Th17 lymphocytes and cytotoxic T lymphocyte infiltration, results in more severe hair loss in patients with chronic AA. IL‐17 may play a more important role in the pathogenesis of chronic AA than IFN‐γ.https://doi.org/10.1002/jvc2.104alopecia areatahair follicleinterleukin 17memory T cellsnatural killer cellsTh 17 cells
spellingShingle Ho‐Jin Kim
Jung‐Hwan Kim
Yu‐Ri Cho
Hyeok‐Jin Kwon
Jung‐Ho Yoon
Ki‐Ho Kim
Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells
JEADV Clinical Practice
alopecia areata
hair follicle
interleukin 17
memory T cells
natural killer cells
Th 17 cells
title Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells
title_full Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells
title_fullStr Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells
title_full_unstemmed Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells
title_short Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells
title_sort predominant expression of interleukin il 17 in chronic alopecia areata compared to ifn γ in pathogenic th17 cells tissue resident memory t cells and natural killer cells
topic alopecia areata
hair follicle
interleukin 17
memory T cells
natural killer cells
Th 17 cells
url https://doi.org/10.1002/jvc2.104
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