ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1565241
This article is part of the Research TopicImmune Microenvironment in hair follicle and sebaceous glands skin diseases: novel findings and future directionsView all articles
Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata
Provisionally accepted
Jesus Gay-Mimbrera1
Pedro Jesus Gomez Arias1,2
Pablo Alvarez-Heredia1
Alexander Batista-Duharte1
Irene Rivera-Ruiz1,2
Macarena Aguilar-Luque1Miguel Juan-Cencerrado1,2
Carmen Mochón-Jiménez1,2Álvaro Cebrián-García1Eloísa Andújar-Pulido3Mónica Pérez-Alegre3
Alejandra Pera1*
Ruano Juan1,2*- 1Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordova, Spain
- 2Department of Dermatology, Reina Sofia University Hospital, Córdoba, Spain
- 3Andalusian Center of Molecular Biology and Regenerative Medicine, Spanish National Research Council (CSIC), Seville, Spain
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Alopecia areata (AA) is an autoimmune disorder causing non-scarring hair loss, ranging from mild to severe forms. Most research has focused on immune dysregulation in the skin, with limited exploration of systemic immune involvement. The role of circulating immune cells in AA pathogenesis remains poorly understood. This study reveals that even mild AA cases display molecular and cellular signs of systemic immune activation. It identifies immune regulatory dysfunction-marked by T cell exhaustion, apoptosis, and senescence-particularly in monocytes, dendritic cells, and double-negative T cells. It highlights systemic immune dysregulation as a core feature of AA, regardless of severity. These findings support early systemic intervention to prevent disease progression. Activation of JAK/STAT pathways in mild AA suggests potential benefit from early use of targeted therapies, including JAK inhibitors. Identifying systemic biomarkers of progression may enable early stratification and personalized treatment.
Keywords: Alopecia Areata, Severity of alopecia tool, Peripheral mononuclear cells, immune pathways, single-cell RNA sequencing, single-cell assaying transposase accessible chromatin sequencing
Received: 22 Jan 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Gay-Mimbrera, Gomez Arias, Alvarez-Heredia, Batista-Duharte, Rivera-Ruiz, Aguilar-Luque, Juan-Cencerrado, Mochón-Jiménez, Cebrián-García, Andújar-Pulido, Pérez-Alegre, Pera and Juan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Alejandra Pera, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordova, 14004, Spain
Ruano Juan, Department of Dermatology, Reina Sofia University Hospital, Córdoba, 14004, Spain
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