CCL22 to Activate Treg Migration and Suppress Depigmentation in Vitiligo Journal Article


Authors: Eby, J. M.; Kang, H. K.; Tully, S. T.; Bindeman, W. E.; Peiffer, D. S.; Chatterjee, S; Le Poole, I. C.; Mehrotra, S
Article Title: CCL22 to Activate Treg Migration and Suppress Depigmentation in Vitiligo
Abstract: In vitiligo, gradual cutaneous depigmentation and cytotoxic T-cell activity against melanocytes are accompanied by a paucity of regulatory T cells (Tregs) in vitiligo patient skin, indicating that autoimmune responses are not adequately held in check. Thus, we sought a means to repopulate patient skin with Tregs. We hypothesized that enhanced expression of CCL22 can promote Treg skin homing to suppress depigmentation. The mouse Ccl22 gene was cloned into an expression vector and resulting DNA was used for gene gun treatment. Two spontaneous depigmentation models with different kinetics of melanocyte loss were utilized, expressing tyrosinase-reactive and gp100-reactive TCR transgenes. Mice were subjected to five gene gun treatments 6 days apart, scanned for depigmentation weekly thereafter, and monitored for activation and proliferation of relevant T cells and for Treg infiltration to the skin. Significantly reduced depigmentation 2 weeks after treatment was accompanied by a markedly increased abundance of Tregs in the skin at the expense of melanocyte-reactive, TCR transgenic T cells, as well as by reduced proliferation and reduced IFN-gamma production in response to cognate peptide. Continued treatment may be necessary for sustained, local immunosuppression. These findings suggest that topical CCL22 may be used for the treatment of vitiligo.
Keywords: Humans; Animals; Mice; Mice, Inbred C57BL; Mice, Transgenic; Transgenes; Cell Proliferation; Immunosuppression; Autoimmunity; Flow Cytometry; Pigmentation; Cell Membrane/metabolism; Monophenol Monooxygenase/metabolism; Biolistics; Chemokine CCL22/metabolism; DNA/chemistry; Hypopigmentation/metabolism; Melanocytes/cytology; Skin/metabolism; Spleen/cytology; T-Lymphocytes, Regulatory/cytology; Vitiligo/metabolism
Journal Title: The Journal of investigative dermatology
Volume: 135
Issue: 6
ISSN: 1523-1747; 0022-202X
Publisher: Unknown  
Journal Place: United States
Date Published: 2015
Start Page: 1574
End Page: 1580
Language: eng
DOI/URL:
Notes: GR: R01AR057643/AR/NIAMS NIH HHS/United States; JID: 0426720; 0 (CCL22 protein, human); 0 (Ccl22 protein, mouse); 0 (Chemokine CCL22); 9007-49-2 (DNA); EC 1.14.18.1 (Monophenol Monooxygenase); 2014/10/05 [received]; 2015/01/13 [revised]; 2015/01/14 [accepted]; 2015/01/09 [aheadofprint]; ppublish