First Author | Rezk AF | Year | 2017 |
Journal | J Invest Dermatol | Volume | 137 |
Issue | 5 | Pages | 1126-1134 |
PubMed ID | 28132854 | Mgi Jnum | J:240868 |
Mgi Id | MGI:5896673 | Doi | 10.1016/j.jid.2016.12.028 |
Citation | Rezk AF, et al. (2017) Misbalanced CXCL12 and CCL5 Chemotactic Signals in Vitiligo Onset and Progression. J Invest Dermatol 137(5):1126-1134 |
abstractText | Generalized nonsegmental vitiligo is often associated with the activation of melanocyte-specific autoimmunity. Because chemokines play an important role in the maintenance of immune responses, we examined chemotactic signatures in cultured vitiligo melanocytes and skin samples of early (</=2 months) and advanced (>/=6 months) vitiligo. Analysis showed that melanocytes in early lesions have altered expression of several chemotaxis-associated molecules, including elevated secretion of CXCL12 and CCL5. Higher levels of these chemokines coincided with prominent infiltration of the skin with antigen presenting cells (APCs) and T cells. Most of the intralesional APCs expressed the CD86 maturation marker and co-localized with T cells, particularly in early vitiligo lesions. These observations were confirmed by in vivo animal studies showing preferential recruitment of APCs and T cells to CXCL12- and CCL5-expressing transplanted melanocytes, immunotargeting of the chemokine-positive cells, continuous loss of the pigment-producing cells from the epidermis, and development of vitiligo-like lesions. Taken together, our studies show that melanocyte-derived CXCL12 and CCL5 support APC and T-cell recruitment, antigen acquisition, and T-cell activation in early vitiligo and reinforce the role of melanocyte-derived CXCL12 and CCL5 in activation of melanocyte-specific immunity and suggest inhibition of these chemotactic axes as a strategy for vitiligo stabilization. |