CXCR3 Blockade Inhibits T Cell Migration Into the Skin and Prevents Development of Alopecia Areata

July 2016 in “ Journal of Immunology ”

Zhijun Dai, Luzhou Xing, Jane E. Cerise, Eddy Hsi Chun Wang, Ali Jabbari, Annemieke de Jong, Lynn Petukhova, Angela M. Christiano, Raphael Clynes

CXCR3 CXCR3 blockade anti-CXCR3 Ab CD8+NKG2D* T cells Alopecia Areata CD8+ T cells CD8+NKG2D+ T cells CD8+CD44 CD62L effector memory T cells IFN-inducible CXCL9 CXCL10 CXCL11 CXCR3 receptor CXCR3 neutralizing antibody AA interferon-inducible chemokines

Studysummary In this study, blocking the CXCR3 receptor in mice prevented the development of alopecia areata by inhibiting the accumulation of specific T cells in the skin, suggesting a potential therapeutic approach for humans. Our plain-language summary of this paper — not a Tressless recommendation.

The study demonstrated that blockade of the CXCR3 receptor by administering a neutralizing antibody (anti-CXCR3 Ab) decreased the accumulation of CD8+NKG2D* T cells in the skin, which in turn prevented the development of Alopecia Areata (AA) in mice. Only 30% of mice treated with anti-CXCR3 Abs developed AA by 12 weeks, compared to control mice. The treatment also resulted in a significant reduction in the number and frequency of CD8+ T cells, particularly CD8+NKG2D+ T cells and CD8+CD44 CD62L effector memory T cells, which are associated with the pathogenesis of AA. Additionally, the expression of IFN-inducible CXCL9, CXCL10, and CXCL11 mRNAs was markedly decreased in the skin. The study involved 5-10 mice per group and the data are representative of two experiments with 10 mice total in each group. The findings suggest that CXCR3 is a key contributor to the pathogenesis of AA and that CXCR3 blockade could be a useful therapeutic target for the treatment of human AA.

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research The C3H/HeJ Mouse and DEBR Rat Models for Alopecia Areata: Review of Preclinical Drug Screening Approaches and Results

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This study reports that C3H/HeJ mice and DEBR rats serve as effective models for screening potential treatments for human alopecia areata, despite certain challenges in predictability and cost.