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

TLDR New treatments for alopecia areata show promise in improving hair loss outcomes.

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”

Clonally expanded CD8+ T cells cause alopecia areata.

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

4 citations , May 2025 in “Frontiers in Immunology”

JAK inhibitors effectively and safely treat alopecia areata with few serious side effects.

research Local Corticosteroids for Alopecia Areata: A Narrative Review

8 citations , May 2025 in “Dermatology and Therapy”

Local corticosteroids can help with alopecia areata, but hair loss often returns after stopping treatment.

research Alopecia Areata: Pathogenesis, Diagnosis, And Therapies

21 citations , April 2025 in “MedComm”

Alopecia areata causes unpredictable hair loss, and more research is needed to fully understand and treat it effectively.

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

April 2025 in “BMC Immunology”

Targeting SIRT1 with antisense oligonucleotides could be a promising treatment for hair loss.

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”

Janus kinase inhibitors are effective and safe for treating Alopecia Areata.

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

March 2025 in “Experimental Dermatology”

Overexpression of IKZF1 and Ikaros causes hair loss in mice similar to alopecia areata.

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”

PPARα agonists may help treat alopecia areata by reducing inflammation.

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

2 citations , December 2024 in “PLoS ONE”

Hematological ratios can effectively predict and manage alopecia areata severity.

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”

Ritlecitinib and baricitinib are similarly effective for hair regrowth in severe alopecia areata.

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

August 2024 in “International Journal of Molecular Sciences”

Mesenchymal Stem Cell therapy shows promise for treating hair loss in Alopecia Areata.

research Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata

August 2024 in “JAMA Dermatology”

Continuous baricitinib is needed to keep hair regrowth in severe alopecia areata.

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

August 2024 in “Allergy”

Alopecia areata patients show increased inflammation and OX40 activation, suggesting a new treatment target.

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”

Deuruxolitinib effectively promotes hair regrowth in adults with alopecia areata.

research Deciphering the Complex Immunopathogenesis of Alopecia Areata

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

Alopecia areata is caused by immune attacks on hair follicles, affecting hair growth and quality of life.

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”

Brepocitinib 30mg is most effective for moderate-to-severe alopecia areata, but ritlecitinib 50mg may offer a better balance of safety and effectiveness.

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”

Baricitinib is effective and safe for long-term use in severe alopecia areata, improving hair regrowth and quality of life with few side effects.

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

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

Dupilumab may help treat alopecia areata without needing high IgE levels.

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

January 2024 in “International Journal of Molecular Sciences”

Blocking the protein CXCL12 with a specific antibody can increase hair growth in common hair loss conditions.

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

4 citations , November 2023 in “Frontiers in immunology”

New treatments targeting T-cell pathways are needed for better alopecia areata management.

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”

CD8+ T cells drive alopecia areata, while regulatory T cells are protective.

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”

Reduced SIRT1 in hair cells may cause alopecia areata by triggering immune responses.

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

May 2023 in “Frontiers in Immunology”

Treg cell-based therapies might help treat hair loss from alopecia areata, but more research is needed to confirm safety and effectiveness.

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 , March 2023 in “American Journal of Clinical Dermatology”

Baricitinib improved severe hair loss in adults over 52 weeks and was safe to use.

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”

ILC1-like cells can independently cause alopecia areata.

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

13 citations , September 2022 in “Frontiers in immunology”

Ifidancitinib, a JAK inhibitor, effectively regrows hair in mice with alopecia by tiring out harmful T cells.

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

40 citations , August 2022 in “Frontiers in immunology”

Blocking JAK/STAT pathways can help treat hair loss from alopecia areata.

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”

Increasing Treg cells in the skin does not cure hair loss from alopecia areata in mice.

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

11 citations , June 2022 in “Frontiers in immunology”

New protein changes may be involved in the immune attack on hair follicles in alopecia areata.

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

37 citations , December 2021 in “Cells”

Alopecia areata severity and treatment response are linked to specific cytokine levels.

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”

Two drugs, ritlecitinib and brepocitinib, improved scalp hair loss condition markers.

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”

Necrostatin-1s can promote hair growth and may help treat 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”

Targeting Vδ1+T-cells may help treat alopecia areata.

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”

The study's results on the effectiveness of low-dose IL-2 for alopecia areata and its impact on immune cells were not provided.

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”

Patients with Alopecia areata have fewer specific immune cells that normally regulate the immune system, which may contribute to the condition.

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”

Alopecia areata involves immune system imbalances that may lead to depression and anxiety.

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

46 citations , October 2018 in “JCI insight”

CD8+ T cells are involved in alopecia areata and may cause 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”

iNKT cells can help prevent and treat alopecia areata by promoting hair regrowth.

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

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

Treating alopecia areata every 3 weeks with diphenylcyclopropenone is more effective than weekly treatments.

research Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth

159 citations , October 2015 in “Science Advances”

Blocking JAK-STAT signaling can lead to hair growth.

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”

Alopecia areata involves immune activation in the scalp, suggesting treatments targeting TH1, TH2, and IL-23 pathways.

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

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

People with alopecia areata have more Th17 cells and fewer Treg cells, which may be key to the condition's development.

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

55 citations , April 2015 in “BMC medicine”

Stem Cell Educator therapy helps regrow hair and improve life quality in alopecia areata patients.

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

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

New genetic discoveries may lead to better treatments for alopecia areata.

research Plasmacytoid Dendritic Cells in Alopecia Areata: Missing Link?

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

Plasmacytoid dendritic cells are a key factor in causing hair loss in alopecia areata and could help differentiate it from other hair loss conditions.

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”

Alopecia areata can be reversed by JAK inhibitors, promoting hair regrowth.

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

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

Nonimmunogenic forms of keratins K71 and K31 can delay and prevent alopecia areata.

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”

Trichohyalin may trigger the immune response causing alopecia areata.

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

717 citations , June 2010 in “Nature”

Alopecia areata involves both innate and adaptive immunity, with specific genes linked to the 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”

Anti-TNF-α therapy may increase the risk of developing alopecia areata, especially in those with a history of autoimmune disease.

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 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”

PPAR alpha may help in hair growth and could be a target for treatment.

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”

Finding eosinophils near hair bulbs helps diagnose alopecia areata.