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-γ 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.
authors: Departments of Pathology, Microbiology and Immunology/ Oncology Research Institute, Loyola University Chicago, Maywood (IL).
authors: Jonathan M
authors: JM
authors: Eby
authors: Departments of Pathology, Microbiology and Immunology/ Oncology Research Institute, Loyola University Chicago, Maywood (IL).
authors: Hee-Kap
authors: HK
authors: Kang
authors: Departments of Pathology, Microbiology and Immunology/ Oncology Research Institute, Loyola University Chicago, Maywood (IL).
authors: Sean T
authors: ST
authors: Tully
authors: Illinois Mathematics and Science Academy, Aurora (IL).
authors: Wendy E
authors: WE
authors: Bindeman
authors: Departments of Pathology, Microbiology and Immunology/ Oncology Research Institute, Loyola University Chicago, Maywood (IL).
authors: Daniel S
authors: DS
authors: Peiffer
authors: Department of Surgery/ Hollings Cancer Center, Medical University of South Carolina, Charleston (SC).
authors: Shilpak
authors: S
authors: Chatterjee
authors: Department of Surgery/ Hollings Cancer Center, Medical University of South Carolina, Charleston (SC).
authors: Shikhar
authors: S
authors: Mehrotra
authors: Departments of Pathology, Microbiology and Immunology/ Oncology Research Institute, Loyola University Chicago, Maywood (IL).
authors: I Caroline
authors: IC
authors: Le Poole
mesh_terms: D000818:Animals; D015551:Autoimmunity; D019470:Biolistics; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D054422:Chemokine CCL22 / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D017496:Hypopigmentation / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D019076:Transgenes; D014820:Vitiligo / Q000378:metabolism*
chemical_list: C515482:CCL22 protein, human; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D004247:DNA; D014442:Monophenol Monooxygenase
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