title: Reduced skin homing by functional Treg in vitiligo.
abstract: In human vitiligo, cutaneous depigmentation involves cytotoxic activity of autoreactive T cells. It was hypothesized that depigmentation can progress in the absence of regulatory T cells (Treg). The percentage of Treg among skin infiltrating T cells was evaluated by immunoenzymatic double staining for CD3 and FoxP3, revealing drastically reduced numbers of Treg in non-lesional, perilesional and lesional vitiligo skin. Assessment of the circulating Treg pool by FACS analysis of CD4, CD25, CD127 and FoxP3 expression, and mixed lymphocyte reactions in presence and absence of sorted Treg revealed no systemic drop in the abundance or activity of Treg in vitiligo patients. Expression of skin homing receptors CCR4, CCR5, CCR8 and CLA was comparable among circulating vitiligo and control Treg. Treg from either source were equally capable of migrating towards CCR4 ligand and skin homing chemokine CCL22, yet significantly reduced expression of CCL22 in vitiligo skin observed by immunohistochemistry may explain failure of circulating, functional Treg to home to the skin in vitiligo. The paucity of Treg in vitiligo skin is likely crucial for perpetual anti-melanocyte reactivity in progressive disease.
authors.affiliation: Departments of Pathology, Microbiology and Immunology/Oncology Institute, Loyola University Chicago, IL, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Klarquist
authors.forename: Cecele J
authors.initials: CJ
authors.lastname: Denman
authors.forename: Claudia
authors.initials: C
authors.lastname: Hernandez
authors.forename: Derek A
authors.initials: DA
authors.lastname: Wainwright
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Wainwright
authors.forename: Faith M
authors.initials: FM
authors.lastname: Strickland
authors.forename: Andreas
authors.initials: A
authors.lastname: Overbeck
authors.forename: Shikar
authors.initials: S
authors.lastname: Mehrotra
authors.forename: Michael I
authors.initials: MI
authors.lastname: Nishimura
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000293:Adolescent; D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D054398:Receptors, CCR4 / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology; D054401:Receptors, CCR8 / Q000276:immunology; D012867:Skin / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology*; D055815:Young Adult
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054401:Receptors, CCR8