Alopecia Areata: From Immunopathogenesis to Emerging Therapeutic Approaches

November 2025 in “ Frontiers in Immunology ”

Su‐Young Kim, Hyun Joo Lee, Jeong Heo, Beom Joon Kim, Joon Seok

alopecia areata autoimmune disorder NKG2D+CD8+ T cells hair follicles JAK inhibitors neutralizing antibodies cytokines chemokines S1P receptor modulators immune cells immunomodulatory strategies AA Janus kinase inhibitors sphingosine-1-phosphate receptor modulators

Studysummary This review discusses the role of immune cells in the pathogenesis of alopecia areata and highlights emerging immunomodulatory strategies and novel therapeutic targets aimed at offering more effective and durable treatments for this autoimmune hair loss disorder.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

Alopecia areata (AA) is an autoimmune disorder causing hair loss, primarily driven by NKG2D<sup>+</sup>CD8<sup>+</sup> T cells targeting hair follicles. Current treatments, including JAK inhibitors, show limited efficacy and high relapse rates. Emerging therapies, such as neutralizing antibodies against cytokines and chemokines, and S1P receptor modulators, offer new hope. The review highlights the importance of understanding immune cell roles in AA and explores novel immunomodulatory strategies and therapeutic targets to improve treatment outcomes.

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research Single-Cell Analysis of Temporal Immune Cell Dynamics in Alopecia Areata Reveals a Causal Role for Clonally Expanded CD8+ T Cells in Disease

4 citations , June 2025 in “Cell Reports”

In this study using the C3H/HeJ mouse model of alopecia areata, researchers found that hyperexpanded CD8⁺ T cell clones were sufficient to initiate disease, establishing a causal link between T cell clonality and pathogenicity.

research Janus Kinase Inhibitors for Alopecia Areata: A Review of Clinical Data

4 citations , May 2025 in “Frontiers in Immunology”

This review examines the mechanisms of Janus kinase inhibitors in treating alopecia areata and evaluates their efficacy and safety, but reports no new clinical results.

research Local Corticosteroids for Alopecia Areata: A Narrative Review

8 citations , May 2025 in “Dermatology and Therapy”

This review discusses the use of topical and intralesional corticosteroids for treating alopecia areata, highlighting their efficacy and safety but noting recurrence and pain as limitations; no new clinical results are reported.

research Alopecia Areata: Pathogenesis, Diagnosis, And Therapies

21 citations , April 2025 in “MedComm”

This review explores the complex factors involved in alopecia areata, such as immune and genetic influences, and discusses advances in diagnostic and therapeutic approaches, while reporting no new clinical results.

research Modulating Immune Responses in Alopecia: Therapeutic Insights and Potential Targets of Antisense Oligonucleotides

April 2025 in “BMC Immunology”

This study highlights the role of immune dysregulation, microRNA modulation, and SIRT1 pathways in alopecia areata, suggesting antisense oligonucleotides targeting miR-485-3p as a promising therapeutic strategy for promoting hair regrowth and reducing inflammation in murine models.

research The Relative Efficacy and Safety of Monotherapies for Alopecia Areata: A Network Meta-Analysis Study

5 citations , April 2025 in “Journal of Cosmetic Dermatology”

This study evaluated eight JAK inhibitor regimens for alopecia areata and provided high-quality evidence on their comparative effectiveness, which can aid clinicians in decision-making and inform medical practice guidelines.

research IKZF1 and Ikaros Overexpression Results in Alopecia Areata-Like Phenotype in Mice

March 2025 in “Experimental Dermatology”

This study found that transgenic mice overexpressing IKZF1 developed lesions similar to alopecia areata, suggesting that Ikaros may play a role in the disease's pathogenesis. Ikaros expression was also higher in human alopecia areata patients compared to controls.

research Patterns of Clinical Response in Patients With Alopecia Areata Treated With Ritlecitinib in the Allegro Clinical Development Programme

13 citations , February 2025 in “Journal of the European Academy of Dermatology and Venereology”

Ritlecitinib shows promise for treating alopecia areata, especially with early and extended treatment.

research Long-Term Safety and Efficacy of Ritlecitinib in Adults and Adolescents with Alopecia Areata and at Least 25% Scalp Hair Loss: Results from the ALLEGRO-LT Phase 3, Open-Label Study

15 citations , January 2025 in “Journal of the European Academy of Dermatology and Venereology”

Ritlecitinib is effective and safe for treating alopecia areata, promoting significant hair regrowth.

research Mechanism of PPARα Agonist in Alopecia Areata

1 citations , January 2025 in “American Journal of Translational Research”

This study found that PPARα agonists provided protective effects in mouse models of alopecia areata by promoting early reversal of the condition and inhibiting T effector cell function, indicating potential therapeutic value for this inflammatory condition.

research Hematological Ratios as an Indicator of Severity in Alopecia Areata: A Retrospective Nationwide Study

2 citations , December 2024 in “PLoS ONE”

This study found that patients with alopecia areata exhibited higher ratios of neutrophils-to-lymphocytes and eosinophils-to-lymphocytes compared to controls, suggesting potential markers for disease prediction and management.

research Systematic Review and Indirect Treatment Comparisons of Ritlecitinib Against Baricitinib in Alopecia Areata

October 2024 in “Journal of the European Academy of Dermatology and Venereology”

This study reported that ritlecitinib 50 mg and baricitinib 4 mg showed similar efficacy in treating severe alopecia areata, with no significant difference in hair regrowth outcomes at Week 24, but there remains considerable uncertainty and a need for further research.

research Mesenchymal Stem Cell Therapy in Alopecia Areata: Visual and Molecular Evidence from a Mouse Model

August 2024 in “International Journal of Molecular Sciences”

In this animal study, researchers found that local administration of mesenchymal stem cell therapy improved hair regrowth and reduced local inflammatory cytokines in mice with Alopecia Areata, although systemic cytokine levels were unchanged.

research Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata

August 2024 in “JAMA Dermatology”

In this study, withdrawal of baricitinib therapy in patients with severe alopecia areata who had achieved hair regrowth led to a loss of benefit in almost all patients, suggesting that continued treatment is necessary to maintain hair regrowth.

research Alopecia Areata Exhibits Cutaneous And Systemic OX40 Activation Across Atopic Backgrounds

August 2024 in “Allergy”

This study identified distinct immune differences in patients with alopecia areata, particularly those with atopic backgrounds, and highlighted the OX40 axis as a potential therapeutic target for the condition.

research Efficacy and Safety of Deuruxolitinib, an Oral Selective Janus Kinase Inhibitor, in Adults with Alopecia Areata: Results from the Phase 3 Randomized, Controlled Trial (THRIVE-AA1)

63 citations , July 2024 in “Journal of the American Academy of Dermatology”

This study found that the oral JAK1/JAK2 inhibitor deuruxolitinib effectively promoted hair regrowth and patient satisfaction in adults with alopecia areata over 24 weeks.

research Deciphering the Complex Immunopathogenesis of Alopecia Areata

45 citations , May 2024 in “International Journal of Molecular Sciences”

This manuscript reviews the latest understanding of alopecia areata's pathogenesis, highlighting the roles of genetic, immunological, and environmental factors, with a focus on immune responses involving IFN-γ and cytotoxic CD8+ T-cells as key contributors to hair follicle inflammation and function disruption without follicle destruction.

Comparative Efficacy and Safety of JAK Inhibitors in the Treatment of Moderate-to-Severe Alopecia Areata: A Systematic Review and Network Meta-Analysis

research Comparative Efficacy and Safety of JAK Inhibitors in the Treatment of Moderate-to-Severe Alopecia Areata: A Systematic Review and Network Meta-Analysis

April 2024 in “Frontiers in pharmacology”

This study compared JAK inhibitors for moderate-to-severe alopecia areata and found brepocitinib 30mg and deuruxolitinib 12mg to be most effective, though deuruxolitinib may cause more adverse events. Further research is needed for long-term efficacy and safety.

research Long-Term Efficacy and Safety of Baricitinib in Patients With Severe Alopecia Areata: 104-Week Results From BRAVE-AA1 and BRAVE-AA2

February 2024 in “Journal of the European Academy of Dermatology and Venereology”

In this study, baricitinib for severe alopecia areata showed sustained efficacy over 104 weeks, with most Week-52 responders maintaining significant hair regrowth and some mixed responders improving further with long-term treatment.

research Dupilumab Therapy for Alopecia Areata: A Case Series and Review of the Literature

15 citations , February 2024 in “Journal of Dermatological Treatment”

This study observed that dupilumab may promote hair regrowth in alopecia areata patients, achieving significant results in a majority of cases without reported adverse events.

research CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and Alopecia Areata

January 2024 in “International Journal of Molecular Sciences”

This study found that subcutaneous injection of a CXCL12 neutralizing antibody significantly promoted hair growth in androgenic alopecia and inhibited hair loss in alopecia areata in mouse models, suggesting its potential as a promising treatment for hair loss.

research Inhibition of T-Cell Activity in Alopecia Areata: Recent Developments and New Directions

4 citations , November 2023 in “Frontiers in immunology”

In this narrative review, researchers outlined the role of T cells in the autoimmune pathogenesis of alopecia areata and highlighted ongoing research into therapeutic pathways, beyond current JAK inhibitors, aimed at developing new treatments for the disease.

research Functional Interrogation of Lymphocyte Subsets in Alopecia Areata Using Single-Cell RNA Sequencing

23 citations , July 2023 in “Proceedings of the National Academy of Sciences”

In this study using a mouse model and human data, researchers found that CD8+ T cells are central to driving alopecia areata, while regulatory T cells offer some protection, highlighting CD8+ T cells as key targets for future therapy development.

research SIRT1 Downregulation Provokes Immune-Inflammatory Responses in Hair Follicle Outer Root Sheath Cells and May Contribute to Development of Alopecia Areata

13 citations , May 2023 in “Journal of Dermatological Science”

This research found that reduced expression of SIRT1 in human scalp tissue may contribute to alopecia areata development by inducing immune-inflammatory responses in hair follicle cells, suggesting that SIRT1 plays a regulatory role in hair follicle immunity.

research The Potential of Regulatory T Cell-Based Therapies for Alopecia Areata

May 2023 in “Frontiers in Immunology”

This article discusses the role of regulatory T cells in alopecia areata, where their deficiency in hair follicles may lead to impaired local immunity and suggests potential therapies like CAR-T reg cells and low-dose IL-2 to alleviate autoimmunity and promote hair regeneration in affected individuals.

research Alopecia Areata: An Updated Review for 2023

91 citations , May 2023 in “Journal of Cutaneous Medicine and Surgery”

Alopecia Areata affects 2% globally, with treatments like essential oils, garlic, and JAK inhibitors showing promise, but more research is needed.

research Efficacy and Safety of Ritlecitinib in Adults and Adolescents With Alopecia Areata: A Randomised, Double-Blind, Multicentre, Phase 2b–3 Trial

227 citations , April 2023 in “The Lancet”

Ritlecitinib effectively treats alopecia areata and is well-tolerated.

research Efficacy and Safety of Baricitinib in Patients with Severe Alopecia Areata Over 52 Weeks in Phase III Trials

20 citations , February 2023 in “American Journal of Clinical Dermatology”

In this study, 40.9% of patients taking 4 mg baricitinib and 21.2% taking 2 mg achieved significant hair regrowth over 52 weeks, indicating potential long-term benefits for adults with severe alopecia areata without introducing new safety concerns.

research Diverse Role of OX40 on T Cells as a Therapeutic Target for Skin Diseases

30 citations , February 2023 in “Journal of Investigative Dermatology”

OX40-targeted therapies may help treat skin diseases by reducing inflammation and balancing immune responses.

research Involvement of ILC1-Like Innate Lymphocytes in Human Autoimmunity: Lessons from Alopecia Areata

18 citations , February 2023 in “eLife”

This study indicates that innate lymphoid cells-type 1 may provoke alopecia areata by disrupting hair follicle immune privilege and inducing characteristic lesions, challenging the view that alopecia areata is purely an autoantigen-dependent, T cell-driven condition.

research Induction of T Cell Exhaustion by JAK1/3 Inhibition in the Treatment of Alopecia Areata

13 citations , September 2022 in “Frontiers in immunology”

This study found that Ifidancitinib, a JAK1/3 inhibitor, significantly promoted hair regrowth and reduced inflammation in a mouse model of alopecia areata by decreasing pathogenic T cell activity and inducing T cell exhaustion.

research An Overview of JAK/STAT Pathways and JAK Inhibition in Alopecia Areata

40 citations , August 2022 in “Frontiers in immunology”

This review discusses the potential of JAK inhibitors as a promising treatment strategy for alopecia areata, highlighting their mechanism and recent FDA approval based on clinical trial efficacy.

research Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice

5 citations , June 2022 in “Frontiers in immunology”

This study observed that expanding regulatory T cells in the skin of mice with alopecia areata did not reverse the condition, indicating that additional immunotherapy may be necessary.

research Autoantigen Discovery in the Hair Loss Disorder, Alopecia Areata: Implications of Post-Translational Modifications

11 citations , June 2022 in “Frontiers in immunology”

This review discusses the challenges in identifying specific hair follicle antigens involved in initiating alopecia areata and highlights the need for further research to understand its etiopathogenesis, reporting no new results.

research The Role of Serum Th1, Th2, and Th17 Cytokines in Patients with Alopecia Areata: Clinical Implications

37 citations , December 2021 in “Cells”

This study found that dysregulation of systemic Th1, Th2, and Th17 cytokines is associated with alopecia areata, with specific cytokines linked to disease activity and treatment response.

research Ritlecitinib And Brepocitinib Demonstrate Significant Improvement In Scalp Alopecia Areata Biomarkers

36 citations , December 2021 in “The journal of allergy and clinical immunology/Journal of allergy and clinical immunology/The journal of allergy and clinical immunology”

This study observed that both ritlecitinib and brepocitinib improved scalp biomarkers in patients with alopecia areata, with associations to hair regrowth seen in this phase 2a trial.

research Alopecia Areata: An Update on Etiopathogenesis, Diagnosis, and Management

290 citations , August 2021 in “Clinical Reviews in Allergy & Immunology”

JAK inhibitors show promise for treating alopecia areata, but more research is needed.

research Hair Growth Promotion by Necrostatin-1s

12 citations , October 2020 in “Scientific Reports”

In this study, Nec-1s was found to promote hair growth and may target necroptosis and the Wnt/β-catenin pathway for potential treatment of hair loss.

research Pro-Inflammatory Vδ1+ T-Cells Infiltrates Are Present In And Around The Hair Bulbs Of Non-Lesional And Lesional Alopecia Areata Hair Follicles

23 citations , September 2020 in “Journal of Dermatological Science”

This pilot study suggests that skin-resident γδT-cells may play a significant role in the early stages of alopecia areata pathogenesis, indicating a potential new target for therapeutic management.

research Low-Dose IL-2 for Treating Moderate to Severe Alopecia Areata: A 52-Week Multicenter Prospective Placebo-Controlled Study Assessing Its Impact on T Regulatory Cell and NK Cell Populations

22 citations , September 2020 in “The journal of investigative dermatology/Journal of investigative dermatology”

This review highlights the possible role of T regulatory cells in the immune-related mechanisms of alopecia areata but reports no new clinical findings.

Alopecia Areata Patients Show Deficiency of FOXP3+CD39+ T Regulatory Cells and Clonotypic Restriction of Treg TCRβ-Chain, Highlighting the Immunopathological Aspect of the Disease

research Alopecia Areata Patients Show Deficiency of FOXP3+CD39+ T Regulatory Cells and Clonotypic Restriction of Treg TCRβ-Chain, Highlighting the Immunopathological Aspect of the Disease

30 citations , July 2019 in “PloS one”

This study found that T-regulatory cells, specifically the FOXP3 CD39 subset, were significantly reduced in both circulation and hair follicles of alopecia areata patients compared to healthy subjects, suggesting potential therapeutic targets.

Alopecia Areata Is Characterized by Dysregulation in Systemic Type 17 and Type 2 Cytokines, Which May Contribute to Disease-Associated Psychological Morbidity

research Alopecia Areata Is Characterized by Dysregulation in Systemic Type 17 and Type 2 Cytokines, Which May Contribute to Disease-Associated Psychological Morbidity

57 citations , April 2019 in “British journal of dermatology/British journal of dermatology, Supplement”

This background review discusses alopecia areata, highlighting the role of CD8+NKG2D+ T cells in hair follicle pathogenesis, and notes that the exact mechanisms causing hair loss remain unclear.

research High-Throughput T Cell Receptor Sequencing Identifies Clonally Expanded CD8+ T Cell Populations in Alopecia Areata

46 citations , October 2018 in “JCI insight”

In this study, the researchers found that treatment with the JAK inhibitor tofacitinib in alopecia areata patients may reduce clonal CD8+ T cell expansions but does not eliminate them entirely, which could contribute to disease relapse.

research An Integrated Model of Alopecia Areata Biomarkers Highlights Both TH1 and TH2 Upregulation

58 citations , July 2018 in “Journal of Allergy and Clinical Immunology”

Alopecia areata severity is linked to increased TH1 and TH2 activity.

research iNKT Cells Ameliorate Human Autoimmunity: Lessons from Alopecia Areata

27 citations , April 2018 in “Journal of autoimmunity”

In this study, iNKT10 cells were found to play a significant role in preventing and treating alopecia areata in a humanized mouse model, suggesting these cells could have potential in managing related autoimmune disorders.

research Efficacy of Diphenylcyclopropenone in Alopecia Areata: A Comparison of Two Treatment Regimens

10 citations , January 2018 in “Postępy Dermatologii i Alergologii”

This study found that 21 out of 39 patients with alopecia areata experienced more than 50% hair regrowth after six months of DPCP treatment, with better outcomes observed in those treated at 3-week intervals compared to weekly intervals.

research Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth

159 citations , October 2015 in “Science Advances”

This study observed that applying JAK-STAT pathway inhibitors to mouse and human skin led to rapid hair growth by inducing the anagen phase of hair follicles.

research Alopecia Areata Profiling Shows TH1, TH2, and IL-23 Cytokine Activation Without Parallel TH17/TH22 Skewing

176 citations , August 2015 in “The journal of allergy and clinical immunology/Journal of allergy and clinical immunology/The journal of allergy and clinical immunology”

This study identified a distinct cytokine activation signature in alopecia areata, involving TH2, TH1, IL-23, and IL-9/TH9 pathways, suggesting potential targeting strategies similar to those in psoriasis and atopic dermatitis.

research Imbalance of T-Helper 17 and Regulatory T Cells in Patients with Alopecia Areata

62 citations , June 2015 in “The Journal of Dermatology”

This study found that patients with alopecia areata had higher levels of Th17 cells and lower levels of regulatory T cells compared to healthy controls, suggesting an immune imbalance in these patients.

research Hair Regrowth in Alopecia Areata Patients Following Stem Cell Educator Therapy

55 citations , April 2015 in “BMC medicine”

This study found that the Stem Cell Educator therapy improved hair regrowth and quality of life in patients with severe alopecia areata by restoring immune balance and protecting hair follicles from autoimmune damage.

research The Genetics Of Alopecia Areata: New Approaches, New Findings, New Treatments

62 citations , January 2015 in “Journal of Dermatological Science”

This review summarizes the current genetic research on alopecia areata, including potential new therapeutic strategies, but reports no new clinical findings.

research Plasmacytoid Dendritic Cells in Alopecia Areata: Missing Link?

45 citations , December 2014 in “Journal of the European Academy of Dermatology and Venereology”

This study found that plasmacytoid dendritic cells are central to the pathogenesis of alopecia areata, suggesting they may help differentiate it from trichotillomania and androgenetic alopecia.

research Diagnostic Usefulness of a Peribulbar Eosinophilic Infiltrate in Alopecia Areata

19 citations , September 2014 in “JAMA Dermatology”

Eosinophilic infiltrate is not a reliable indicator for diagnosing chronic alopecia areata.

research Alopecia Areata Is Driven by Cytotoxic T Lymphocytes and Is Reversed by JAK Inhibition

701 citations , August 2014 in “Nature medicine”

This study found that JAK inhibitors promote hair regrowth in both mice and human alopecia areata cases by blocking key immune pathways involved in disease development.

research Tolerance Induction by Hair-Specific Keratins in Murine Alopecia Areata

18 citations , July 2013 in “Journal of Leukocyte Biology”

The study suggests that vaccination with soluble keratin peptides K71 and K31 significantly delayed the onset and progression of autoimmune alopecia areata in mice by inducing T cell anergy.

research Histologic Features of Alopecia Areata Other Than Peribulbar Lymphocytic Infiltrates

53 citations , September 2011

Other common signs, not just the well-known immune cells around hair bulbs, are important for diagnosing hair loss from alopecia areata.

research Trichohyalin Is a Potential Major Autoantigen in Human Alopecia Areata

66 citations , July 2010 in “Journal of Proteome Research”

This study suggests that an immune response to trichohyalin and keratin 16 may contribute to the pathogenesis of alopecia areata.

research Genome-Wide Association Study in Alopecia Areata Implicates Both Innate and Adaptive Immunity

717 citations , June 2010 in “Nature”

This study identified key genetic regions associated with alopecia areata, highlighting both acquired and innate immune involvement, with a novel link to the upregulation of ULBP ligands in autoimmune disease.

research Alopecia Areata as Another Immune-Mediated Disease Developed in Patients Treated with Tumor Necrosis Factor-Alpha Blocker Agents

61 citations , June 2010 in “Journal of the European Academy of Dermatology and Venereology”

This study highlights cases of alopecia areata that developed during anti-TNF-α therapy, suggesting a potential link or increased frequency, particularly among individuals with a personal or family history of autoimmune diseases.

research Experimental Evaluation of Ebastine, a Second-Generation Antihistamine, as a Supportive Medication for Alopecia Areata

35 citations , March 2010 in “Journal of Dermatological Science”

Ebastine may help regrow hair in alopecia areata patients.

research Maintenance of Hair Follicle Immune Privilege Is Linked to Prevention of NK Cell Attack

253 citations , December 2007 in “Journal of Investigative Dermatology”

This study suggests that human hair follicles may actively suppress natural killer cells, which contrasts with the observed defects in NK cell regulation in alopecia areata.

research Recurrence of Alopecia Areata in a Patient Receiving Etanercept Injections

75 citations , June 2005 in “Archives of Dermatology”

In this case report, a patient experienced a recurrence of alopecia areata while undergoing etanercept treatment, suggesting the drug may not effectively prevent this condition's return.

research Characterization of Hair Follicle Antigens Targeted by the Anti-Hair Follicle Immune Response

148 citations , September 2003 in “Journal of Investigative Dermatology Symposium Proceedings”

Alopecia areata is an autoimmune disorder causing hair loss, linked to specific hair follicle antigens and genetic factors.

research Expression of Peroxisome Proliferator Activated Receptors (PPARs) in Human Hair Follicles and PPARα Involvement in Hair Growth

51 citations , September 2000 in “Acta dermato-venereologica”

This study found that PPAR alpha, -delta, and -gamma are expressed in human hair follicle cells, and clofibrate exhibited a beneficial effect on hair follicle survival in culture within a specific concentration range.

research Eosinophils in Fibrous Tracts and Near Hair Bulbs: A Helpful Diagnostic Feature of Alopecia Areata

22 citations , February 2000 in “Journal of the American Academy of Dermatology”

Eosinophils are not a reliable marker for diagnosing alopecia areata.

research Eosinophils in Fibrous Tracts and Near Hair Bulbs: A Helpful Diagnostic Feature of Alopecia Areata

64 citations , July 1997 in “Journal of The American Academy of Dermatology”

This study found that eosinophils are a useful diagnostic feature for alopecia areata, especially when the typical "swarm of bees" lymphoid infiltrate is absent, helping differentiate it from trichotillomania.