Journal article
CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata
The Journal of immunology (1950), Vol.197(4), pp.1089-1099
08/15/2016
DOI: 10.4049/jimmunol.1501798
PMCID: PMC5031416
PMID: 27412416
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-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 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.
Details
- Title: Subtitle
- CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata
- Creators
- Zhenpeng Dai - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032Luzhou Xing - Department of Pathology, Columbia University, New York, NY 10032; andJane Cerise - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032Eddy Hsi Chun Wang - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032Ali Jabbari - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032Annemieke de Jong - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032Lynn Petukhova - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032Angela M Christiano - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032 amc65@cumc.columbia.eduRaphael Clynes - Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.197(4), pp.1089-1099
- DOI
- 10.4049/jimmunol.1501798
- PMID
- 27412416
- PMCID
- PMC5031416
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- T32 GM008224 / NIGMS NIH HHS P30 AR044535 / NIAMS NIH HHS R01 AR065963 / NIAMS NIH HHS R03 AR064014 / NIAMS NIH HHS K08 AR069111 / NIAMS NIH HHS
- Language
- English
- Date published
- 08/15/2016
- Academic Unit
- Dermatology
- Record Identifier
- 9984025414402771
Metrics
14 Record Views