TY - JOUR
T1 - Reduced skin homing by functional Treg in vitiligo
AU - Klarquist, Jared
AU - Denman, Cecele J.
AU - Hernandez, Claudia
AU - Wainwright, Derek J.
AU - Strickland, Faith M.
AU - Overbeck, Andreas
AU - Mehrotra, Shikar
AU - Nishimura, Michael I.
AU - Le Poole, I. Caroline
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Autoimmune
KW - Depigmentation
KW - T cells
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=77949409205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949409205&partnerID=8YFLogxK
U2 - 10.1111/j.1755-148X.2010.00688.x
DO - 10.1111/j.1755-148X.2010.00688.x
M3 - Article
C2 - 20175879
AN - SCOPUS:77949409205
SN - 1755-1471
VL - 23
SP - 276
EP - 286
JO - Pigment Cell and Melanoma Research
JF - Pigment Cell and Melanoma Research
IS - 2
ER -
