Dataset Information

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

ABSTRACT: Alopecia areata (AA) is an autoimmune disease of the hair follicle that results in hair loss of varying severity. Recently, we showed that IFN-?-producing NKG2D(+)CD8(+) T cells actively infiltrate the hair follicle and are responsible for its destruction in C3H/HeJ AA mice. Our transcriptional profiling of human and mouse alopecic skin showed that the IFN pathway is the dominant signaling pathway involved in AA. We showed that IFN-inducible chemokines (CXCL9/10/11) are markedly upregulated in the skin of AA lesions, and further, that the IFN-inducible chemokine receptor, CXCR3, is upregulated on alopecic effector T cells. To demonstrate whether CXCL9/10/11 chemokines were required for development of AA, we treated mice with blocking Abs to CXCR3, which prevented the development of AA in the graft model, inhibiting the accumulation of NKG2D(+)CD8(+) T cells in the skin and cutaneous lymph nodes. These data demonstrate proof of concept that interfering with the Tc1 response in AA via blockade of IFN-inducible chemokines can prevent the onset of AA. CXCR3 blockade could be approached clinically in human AA with either biologic or small-molecule inhibition, the latter being particularly intriguing as a topical therapeutic.

SUBMITTER: Dai Z

PROVIDER: S-EPMC5031416 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Dai Zhenpeng Z Xing Luzhou L Cerise Jane J Wang Eddy Hsi Chun EH Jabbari Ali A de Jong Annemieke A Petukhova Lynn L Christiano Angela M AM Clynes Raphael R

Journal of immunology (Baltimore, Md. : 1950) 20160713 4

Alopecia areata (AA) is an autoimmune disease of the hair follicle that results in hair loss of varying severity. Recently, we showed that IFN-γ-producing NKG2D(+)CD8(+) T cells actively infiltrate the hair follicle and are responsible for its destruction in C3H/HeJ AA mice. Our transcriptional profiling of human and mouse alopecic skin showed that the IFN pathway is the dominant signaling pathway involved in AA. We showed that IFN-inducible chemokines (CXCL9/10/11) are markedly upregulated in t ...[more]

PMID: 27412416

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Project description:IntroductionIndividuals with alopecia areata (AA) may experience significant impacts on their health-related quality of life. The novel Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire has been developed to assess hair loss signs, emotional symptoms, and activity limitations associated with AA. The objective of this study was to evaluate psychometric properties and establish scoring of the AAPPO in adults and adolescents with AA.MethodsScoring and measurement properties of the AAPPO were examined using baseline and 2-week follow-up data from a prospective, noninterventional, web-based study of 121 patients with AA (85 adults aged ≥ 18 years, 36 adolescents aged 12-17 years) with Severity of Alopecia Tool (SALT) ≥ 25% scalp hair loss.ResultsExploratory and confirmatory factor analysis supported four single Hair Loss (HL) items, an Emotional Symptoms domain (ES; 4 items), and an Activity Limitations domain (AL; 3 items). Among all patients, the multi-item ES and AL domains had strong internal consistency (α ≥ 0.87); all HL items and domain scores had strong test-retest reliability (weighted kappa or intraclass correlation coefficients ≥ 0.78). All HL item scores demonstrated strong construct validity (r ≥ 0.52) compared with the patient-reported Alopecia Areata Symptom and Impact Scale (AASIS) hair loss subscale score; ES and AL domain scores exhibited strong construct validity (r ≥ 0.66) compared with the SF-36 Mental Component Summary (MCS) score. Using SALT scores, HL mean item scores were better (lower) in the 25-49% SALT subgroup versus those with highest SALT scores (76-100%); however, ES mean domain scores were better in the SALT 76-100% subgroup in the same comparison (p < 0.0001). Using AASIS and MCS score-created subgroups, ES and AL mean domain scores demonstrated hypothesized differences across subgroups (all p values < 0.0001).ConclusionThe AAPPO questionnaire is a reliable, valid disease-specific measure of hair loss severity and impact in individuals with AA.

Dataset Information

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

Publications

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

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