title: Misbalanced CXCL12 and CCL5 Chemotactic Signals in Vitiligo Onset and Progression.
abstract: 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.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Dermatology, Minia University, Minia, Egypt.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Rezk
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Daria Marley
authors.initials: DM
authors.lastname: Kemp
authors.affiliation: Department of Dermatology, Minia University, Minia, Egypt.
authors.forename: Moetaz
authors.initials: M
authors.lastname: El-Domyati
authors.affiliation: Department of Dermatology, Minia University, Minia, Egypt.
authors.forename: Wael Hosam
authors.initials: WH
authors.lastname: El-Din
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Igoucheva
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: vitali.alexeev@jefferson.edu.
authors.forename: Vitali
authors.initials: V
authors.lastname: Alexeev
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity; D002460:Cell Line; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D014820:Vitiligo / Q000276:immunology / Q000473:pathology*
chemical_list: D018946:Chemokine CCL5; D054377:Chemokine CXCL12