What question did this study set out to answer?

This research aims to determine whether the activation of resident T cells in hair follicles contributes to immune privilege loss that leads to alopecia areata.

May 3, 2026SHILAP Revista de lepidopterología0 citationsOpen Access

Resident T cell activation leads to human hair follicle immune privilege loss ex vivo, which is prevented by the DHODH inhibitor farudodstat: relevance for alopecia areata

IPIlaria Piccini TRThomas Rouillé WFWolfgang Funk

Key Points

This research aims to determine whether the activation of resident T cells in hair follicles contributes to immune privilege loss that leads to alopecia areata.
Utilized human microdissected hair follicle organ culture model
Activated intra- and peri-follicular T cells with αCD3/αCD28 antibodies
Co-administered DHODH inhibitor farudodstat to assess its effects on T cell activation.
TCR stimulation resulted in increased CD3+Ki-67+ cell numbers and enhanced T cell proliferation.
Farudodstat treatment reduced T cell proliferation and decreased MHC class I and II expression induced by TCR stimulation.
Stimulation of resident T cells led to an alopecia areata-like phenotype characterized by immune privilege collapse.

Abstract

The autoimmune hair loss disorder alopecia areata (AA), is characterized by immune privilege (IP) collapse of the hair follicle (HF) bulb resulting from a Th1-dependent inflammatory response. Although CD8+ T cells are recognized key drivers of the disease, it remains to be clarified whether the activation of HF resident T cells suffice to initiate IP loss and thus elicit the cascade of events leading to AA. Here, we utilized the human microdissected HF organ culture model to answer this question by activating intra- and peri-follicular HF resident T cells with αCD3/αCD28 antibodies. TCR stimulation indeed resulted in enhanced resident T cell proliferation, as indicated by significantly increased CD3+Ki-67+ cells, and higher intrafollicular CD3+ T cell numbers. Furthermore, αCD3/αCD28 stimulation promoted key signs of HF IP collapse, by increasing bulbar MHC class I and II expression and elevating MHC class II+ cells numbers. We next sought to investigate whether T cell proliferation plays a central role in the TCR activation–dependent collapse of the bulb IP. To test this, we co-administered the DHODH inhibitor farudodstat 1 day prior and during the stimulation with αCD3/αCD28 in HF organ culture. Short-term treatment with farudodstat reduced the increase in T cell proliferation and significantly decreased the upregulated MHC class I and II expression induced by TCR stimulation with αCD3/αCD28. Our results show that stimulation of HF resident T cells via TCR engagement induces an AA–like phenotype in healthy human HFs ex vivo, characterized by T cell proliferation and subsequent IP collapse. DHODH inhibition with farudodstat only partially reduces T cell numbers but prevented HF IP collapse induction.

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