Human Regulatory Gamma Delta T Lymphocytes as Novel Autoimmunity-Protective Cells: Lessons from Alopecia Areata

November 2024

Amos Gilhar, Aviad Keren, Nyra Goldstein, Marta Bertolini, Riad Kassem, Assaf Zeltzer, Nataša Štrbo, Ralf Paus

γδT lymphocytes γδTregs alopecia areata autoimmune hair loss IL-2 IL-15 zoledronate lymphocytic infiltration hair follicle immune privilege keratinocyte proliferation IL-10 TGF-β1 CD8+ T cells gamma delta T cells interleukin-2 interleukin-15 Zometa immune privilege transforming growth factor beta 1

Studysummary This study found that γδTregs can prevent and treat alopecia areata in a mouse model with human scalp transplants, suggesting potential for cell-based therapies in autoimmune diseases like alopecia.

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This study investigates the role of human regulatory γδT cells (γδTregs) in alopecia areata (AA), a common autoimmune hair loss disorder. The research found that γδTregs are more prevalent in lesional AA skin compared to non-lesional or healthy skin. In experiments using human scalp skin xenotransplants on mice, γδTregs, pre-activated with IL-2, IL-15, and zoledronate, were able to prevent AA lesion development and promote hair regrowth by reducing lymphocytic infiltration and restoring hair follicle immune privilege. Additionally, γδTregs co-cultured with stressed human scalp hair follicles mitigated immune privilege collapse and enhanced keratinocyte proliferation, primarily through IL-10 and TGF-β1 secretion. These findings suggest that γδTregs could be a novel therapeutic target for CD8+ T cell-dependent autoimmune diseases like AA.

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This study examines the similarities and differences in the pathogenesis of autoimmune conditions alopecia areata and vitiligo, highlighting shared features like immune cell involvement and cytokine pathways, while noting differing immune responses in skin and hair.

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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.

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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.

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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.

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Ex Vivo Treatment with Allogenic Mesenchymal Stem Cells on Peripheral Blood Mononuclear Cells of Patients with Severe Alopecia Areata

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37 citations , August 2022 in “Frontiers in pharmacology”

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This study found that human dermal γδT-cells can act as stress sentinels and potentially trigger autoimmune responses toward stressed hair follicles, resembling features of alopecia areata.

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134 citations , July 2020 in “Experimental dermatology”

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

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56 citations , January 2019 in “Lancet”

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