Frontiers in Alopecia Areata Pathobiology Research

October 2019 in “ The journal of allergy and clinical immunology/Journal of allergy and clinical immunology/The journal of allergy and clinical immunology ”

Amos Gilhar, Rimma Laufer-Britva, Aviad Keren, Ralf Paus

alopecia areata CD8+ T cells natural killer cells NK cells unconventional T cells IFN-γ regulatory lymphocyte subsets hair follicle immune privilege immune privilege immunotherapies autoimmune disorders AA IP

Studysummary This review discusses emerging research areas in alopecia areata pathobiology, highlighting the potential roles of unconventional immune cells and the need for more targeted therapeutic strategies, but reports no new experimental results.

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

The review highlighted emerging areas in alopecia areata (AA) pathobiology, suggesting that CD8+ T cells were not the sole drivers of the disease. Instead, subsets of natural killer (NK) and unconventional T cells, which produced IFN-γ, might also have contributed independently of classical CD8+ T-cell functions. Additionally, regulatory lymphocyte subsets played a crucial role in maintaining hair follicle immune privilege (IP), and their dysfunction in AA patients could be a therapeutic target. The review emphasized the need for further research into these new players and mechanisms to develop innovative immunotherapies for AA and potentially other autoimmune disorders.

View this study on jacionline.org →

Discuss this study in the Community →

Research cited in this study

49 / 49 results

research Apremilast and Tofacitinib Exert Differential Effects in the Humanized Mouse Model of Alopecia Areata

5 citations , June 2019 in “British Journal of Dermatology”

No results are provided in this article as it lacks an available abstract, making it unclear what effects apremilast and tofacitinib have in a humanized mouse model of alopecia areata.

research Possible Role of ILC1 in the Pathogenesis of Alopecia Areata

3 citations , April 2019 in “The journal of investigative dermatology/Journal of investigative dermatology”

This research suggests that innate lymphoid cells type 1 (ILC1) may contribute to the development of alopecia areata, alongside CD8+ T cells, by disrupting hair follicle immune privilege and promoting features of the disease.

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 New Drugs Under Investigation for the Treatment of Alopecias

26 citations , January 2019 in “Expert Opinion on Investigational Drugs”

This review explored the new and emerging treatments for androgenetic alopecia and alopecia areata, finding that JAK inhibitors show promise for alopecia areata, while advancements in stem-cell research may eventually lead to new and improved treatments for androgenetic alopecia.

research Tofacitinib Therapy for Children with Severe Alopecia Areata

39 citations , January 2019 in “Journal of the American Academy of Dermatology”

In this study, three children with severe alopecia treated with systemic tofacitinib showed significant hair regrowth, suggesting it may be a potential option for those unresponsive to conventional therapy.

research JAK Inhibitors and Alopecia Areata

56 citations , January 2019 in “Lancet”

This review discusses the emerging use of JAK inhibitors in alopecia areata treatment and reports no new clinical results; it highlights hair regrowth despite symptom recurrence after stopping therapy.

research Alopecia Areata in Severe Atopic Dermatitis Treated With Dupilumab

49 citations , December 2018 in “Journal of Investigational Allergology and Clinical Immunology”

Dupilumab may cause hair loss in some patients with severe atopic dermatitis.

A Randomized Placebo-Controlled Single-Center Pilot Study of the Safety and Efficacy of Apremilast in Subjects with Moderate-to-Severe Alopecia Areata

research A Randomized Placebo-Controlled Single-Center Pilot Study of the Safety and Efficacy of Apremilast in Subjects with Moderate-to-Severe Alopecia Areata

42 citations , November 2018 in “Archives of dermatological research”

Apremilast was not effective in treating moderate-to-severe alopecia areata.

research Response to Ustekinumab in Three Pediatric Patients with Alopecia Areata

25 citations , October 2018 in “Pediatric dermatology”

In this study, three pediatric patients with alopecia areata demonstrated hair regrowth after being treated with ustekinumab.

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 Rethinking The Classification Of Alopecia Areata

13 citations , September 2018 in “Journal of the American Academy of Dermatology”

This editorial proposes a new classification for alopecia areata that incorporates the SALT score and body hair involvement, aiming to improve the assessment and treatment outcomes.

research Ruxolitinib for the Treatment of Severe Alopecia Areata

37 citations , September 2018 in “Journal of the American Academy of Dermatology”

This letter reports a series of cases where the use of ruxolitinib at a lower dose than previously studied led to hair regrowth in patients with severe alopecia areata.

research JAK Inhibitors for Treatment of Alopecia Areata

63 citations , July 2018 in “The journal of investigative dermatology/Journal of investigative dermatology”

In this review, the researchers reported that JAK inhibitors, originally approved by the FDA for other uses, have shown effectiveness in reversing hair loss in patients with moderate to severe alopecia areata, based on current preclinical and clinical studies.

research Comorbidities in Alopecia Areata: A Systematic Review and Meta-Analysis

100 citations , July 2018 in “Journal of The American Academy of Dermatology”

This study found that alopecia areata is linked with a higher prevalence of systemic and psychiatric diseases, suggesting that physicians should monitor for these potential comorbidities.

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 Alopecia Areata and the Gut: The Link Opens Up for Novel Therapeutic Interventions

48 citations , May 2018 in “Expert Opinion on Therapeutic Targets”

This review discusses how modern lifestyle factors affecting gut health may contribute to Alopecia Areata in genetically predisposed individuals, reporting no new results but suggesting the need for long-term interventions.

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 Alopecia Areata After Dupilumab for Atopic Dermatitis

53 citations , January 2018 in “JAAD case reports”

This report describes the case of a patient who developed alopecia areata within five weeks of starting treatment for atopic dermatitis with dupilumab.

research Novel Therapies for Alopecia Areata: The Era of Rational Drug Development

9 citations , December 2017 in “The Journal of Allergy and Clinical Immunology”

This review discusses the evolution of alopecia areata treatments towards more targeted therapies and reports no new clinical results, emphasizing cooperation between clinicians and scientists in understanding the disease's pathophysiology.

research Hair Follicle Immune Privilege Revisited: The Key to Alopecia Areata Management

102 citations , December 2017 in “The journal of investigative dermatology. Symposium proceedings/The Journal of investigative dermatology symposium proceedings”

This review discusses the role of immune privilege collapse in the pathogenesis of alopecia areata, emphasizing the potential for therapeutic manipulation of hair bulb immune privilege to offer new treatment options, and reports no new results.

research Alopecia Areata: Overview and Insights from January 2018

290 citations , December 2017 in “Journal of The American Academy of Dermatology”

This article reviews the epidemiology, clinical evaluation, and pathogenesis of alopecia areata and highlights recent advancements, but it does not report new clinical findings.

research SOCS3 Treatment Prevents the Development of Alopecia Areata by Inhibiting CD8+ T Cell-Mediated Autoimmune Destruction

16 citations , March 2017 in “Oncotarget”

This study suggests that SOCS3 treatment may effectively inhibit alopecia areata by suppressing CD8+ T cell activity and IFN-γ production.

research Safety and Efficacy of the JAK Inhibitor Tofacitinib Citrate in Patients with Alopecia Areata

222 citations , September 2016 in “JCI insight”

This research overview highlights that although JAK inhibitors show promise as potential treatments for alopecia areata based on recent insights into the disease mechanism, their efficacy has not yet been thoroughly evaluated in a systematic manner.

research Successful Hair Regrowth in an Acute Diffuse Form of Alopecia Areata During Oral Tacrolimus Treatment in a Patient With Rheumatoid Arthritis

8 citations , August 2016 in “Journal of the European Academy of Dermatology and Venereology”

Oral tacrolimus helped a rheumatoid arthritis patient regrow hair lost due to alopecia areata.

research Genomewide Analysis of Copy Number Variants in Alopecia Areata in a Central European Cohort Reveals Association with MCHR2

29 citations , June 2016 in “Experimental Dermatology”

This study provides suggestive evidence that duplications in the MCHR2 gene may be involved in the pathogenesis of alopecia areata.

research ULBP3: A Marker for Alopecia Areata Incognita

15 citations , May 2016 in “Archives of Dermatological Research”

This study found significantly higher levels of the protein ULBP3 in patients with alopecia areata incognita compared to other hair loss conditions and healthy controls, suggesting ULBP3's potential as a diagnostic marker for AAI.

research Gamma Delta T Cells as Novel Players in Alopecia Areata Pathobiology: Vdelta1 Positive T Lymphocytes May Recognize Stressed Hair Follicle Keratinocytes, Leading to IFN Gamma-Dependent Hair Follicle Dystrophy and Immune Privilege Collapse

1 citations , April 2016 in “Journal of Investigative Dermatology”

This study suggests that NKG2D+ Vδ1 T cells may contribute to hair follicle pathology in alopecia areata by recognizing stressed keratinocytes and inducing immune privilege collapse.

Vasoactive Intestinal Peptide, Whose Receptor-Mediated Signaling May Be Defective in Alopecia Areata, Provides Protection from Hair Follicle Immune Privilege Collapse

research Vasoactive Intestinal Peptide, Whose Receptor-Mediated Signaling May Be Defective in Alopecia Areata, Provides Protection from Hair Follicle Immune Privilege Collapse

36 citations , April 2016 in “British journal of dermatology/British journal of dermatology, Supplement”

This article reviews the role of vasoactive intestinal peptide in maintaining immune privilege in hair follicles and does not report new findings; the authors propose it as essential for immune homeostasis in alopecia areata.

research Alopecia Areata: Animal Models Illuminate Autoimmune Pathogenesis and Novel Immunotherapeutic Strategies

82 citations , March 2016 in “Autoimmunity reviews”

This review explores animal models of alopecia areata, particularly focusing on the insights they've provided into the disease's immune mechanisms and potential treatment approaches, without reporting new experimental data.

research Laser Capture Microdissection Reveals Transcriptional Abnormalities In Alopecia Areata Before, During, And After Active Hair Loss

16 citations , December 2015 in “Journal of Investigative Dermatology”

This study found significant gene expression abnormalities in hair follicles affected by alopecia areata, suggesting persistent changes that may predispose to future relapses even after hair regrowth.

research Biomarkers of Alopecia Areata Disease Activity and Response to Corticosteroid Treatment

65 citations , December 2015 in “Experimental dermatology”

This study found that both Th1 and Th2 immune responses, along with IL-23 and IL-32 cytokine pathways, are active in alopecia areata lesions, and corticosteroid injections significantly altered these immune markers.

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 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 Mechanisms Regulating Skin Immunity and Inflammation

610 citations , April 2014 in “Nature Reviews Immunology”

This review discusses the complex mechanisms regulating skin immunity to balance host defense with inflammation, but reports no new findings.

research Hair Follicle Mesenchyme-Associated PD-L1 Regulates T-Cell Activation Induced Apoptosis: A Potential Mechanism of Immune Privilege

53 citations , September 2013 in “Journal of Investigative Dermatology”

This study suggests that cultured hair follicle dermal sheath cup cells exhibit immune privilege properties, partly through the expression of PD-L1, which impacts co-cultured immune cells' behavior.

research Birth, Life, and Death of the MAGE3 Hypothesis of Alopecia Areata Pathobiology

12 citations , August 2013 in “Journal of Dermatological Science”

This article shares the researchers' challenging journey in exploring the pathobiology of alopecia areata and reports no definitive clinical advances.

research Blocking Potassium Channels (Kv1.3): A New Treatment Option for Alopecia Areata?

28 citations , March 2013 in “Journal of Investigative Dermatology”

Kv1.3 blockers may help treat alopecia areata and promote hair regrowth.

research Autoimmune Disease Induction in a Healthy Human Organ: A Humanized Mouse Model of Alopecia Areata

75 citations , October 2012 in “Journal of Investigative Dermatology”

This study developed an animal model that recreates alopecia areata by injecting healthy human skin grafts in immunocompromised mice with peripheral blood mononuclear cells enriched for NKG2D+ and CD56+ cells.

research Alopecia Areata: An Autoimmune Disease Causing Hair Loss

421 citations , April 2012 in “The New England Journal of Medicine”

Alopecia Areata is an autoimmune condition causing hair loss with no cure and treatments that often don't work well.

research Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

21 citations , June 2011 in “Investigative Ophthalmology & Visual Science”

This article argues that human scalp hair follicles could serve as a surrogate model for studying immune privilege in the human eye, offering a novel approach for ocular IP research.

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 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 Probing the Effects of Stress Mediators on the Human Hair Follicle

159 citations , November 2007 in “American Journal of Pathology”

In this study, researchers found that substance P triggered premature catagen development and immune changes in human scalp hair follicles, providing a possible biological link between stress and hair loss conditions like telogen effluvium and alopecia areata.

research Failure to Induce Alopecia Areata in C3H/HeJ Mice with Exogenous Interferon Gamma

13 citations , December 2006 in “Journal of experimental animal science”

This study found that injecting interferon gamma into C3H/HeJ mice did not alter the frequency or onset of alopecia areata, suggesting the protein alone does not trigger the disease.

research Transient CD44 Variant Isoform Expression and Reduction in CD4+/CD25+ Regulatory T Cells in C3H/HeJ Mice with Alopecia Areata

77 citations , June 2002 in “Journal of Investigative Dermatology”

CD44 variant changes start alopecia areata, but don't maintain it.

research Hair Growth Inhibition by Heparin in Mice: A Model System for Studying the Modulation of Epithelial Cell Growth by Glycosaminoglycans

46 citations , May 1991 in “British Journal of Dermatology”

In this study, heparin was found to exert dose- and hair cycle-dependent effects on skin epithelial cells in mice, affecting hair follicle development and protein synthesis differently based on its administration method.