T H 1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Samuel J Connell; Sydney Crotts; Ryan Reis; Maddison M Lensing; Payton Kahl; Nicholas Henderson; Otgonzaya Ayush; Zhaowen Zhu; Luana S Ortolan; Audrey C Ko; Erin M Shriver; Keith D Carter; John T Harty; Joan M Goverman; Ali Jabbari

doi:10.1126/sciadv.adz2257

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T H 1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Journal article

Open access

Peer reviewed

T H 1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Samuel J Connell, Sydney Crotts, Ryan Reis, Maddison M Lensing, Payton Kahl, Nicholas Henderson, Otgonzaya Ayush, Zhaowen Zhu, Luana S Ortolan, Audrey C Ko, …

Science advances, Vol.11(44), eadz2257

10/31/2025

DOI: 10.1126/sciadv.adz2257

PMCID: PMC12577704

PMID: 41171930

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Abstract

Alopecia areata (AA) is an autoimmune disease defined by hair loss and peribulbar infiltrate of CD8 and CD4 T cells. Prior studies have focused on the role of CD8 T cells in the development of AA. Multiple roles for CD4 T cell help have been demonstrated for support of CD8 T cell responses; however, the role of CD4 T cells in AA remains unclear. Here, we demonstrate that CD4 T cells from the skin-draining lymph nodes (SDLNs) of AA mice transferred disease to recipient mice. These cells exhibited a T helper type 1 (T 1) effector transcriptional and phenotypic profile, and their pathogenic activity required endogenous CD8 T cells and host IFN-γ responsiveness. Targeted deletion of CD4 T cell-mediated production of IFN-γ abrogated the ability of this cell population to transfer disease. Together, these data provide mechanistic insights into pathways driving AA development, strengthening our understanding of the disease and inviting studies into exploring alternative therapeutic strategies for human patients.

Alopecia Areata - etiology

Alopecia Areata - immunology

Alopecia Areata - metabolism

Alopecia Areata - pathology

Animals

CD4-Positive T-Lymphocytes - immunology

CD4-Positive T-Lymphocytes - metabolism

CD8-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - metabolism

Disease Models, Animal

Humans

Interferon-gamma - immunology

Interferon-gamma - metabolism

Lymph Nodes - immunology

Mice

Mice, Inbred C57BL

Th1 Cells - immunology

Th1 Cells - metabolism

Details

Title: Subtitle: T H 1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata
Creators: Samuel J Connell - University of Iowa
Sydney Crotts - University of Iowa
Ryan Reis - University of Iowa
Maddison M Lensing - University of Iowa
Payton Kahl - University of Iowa
Nicholas Henderson - University of Iowa
Otgonzaya Ayush - University of Iowa
Zhaowen Zhu - University of Iowa
Luana S Ortolan - University of Iowa
Audrey C Ko - University of Iowa
Erin M Shriver - University of Iowa
Keith D Carter - University of Iowa
John T Harty - University of Iowa
Joan M Goverman - University of Washington
Ali Jabbari - Iowa City VA Health Care System
Resource Type: Journal article
Publication Details: Science advances, Vol.11(44), eadz2257
DOI: 10.1126/sciadv.adz2257
PMID: 41171930
PMCID: PMC12577704
NLM abbreviation: Sci Adv
ISSN: 2375-2548
eISSN: 2375-2548
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Grant note: R01 AR077194 / NIAMS NIH HHS I01 BX004907 / BLRD VA S10 OD034193 / NIH HHS T32 AI007485 / NIAID NIH HHS K08 AR069111 / NIAMS NIH HHS
Language: English
Date published: 10/31/2025
Academic Unit: Dermatology; Pathology; Neuroscience and Pharmacology; Otolaryngology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9985024266002771

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