Related Experiment Video
Updated: Nov 3, 2025
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
CCL17-CCR4 axis contributes to the onset of vitiligo in mice
He Li1, Congpin Wang2, Xiaoqing Li1
1Department of Dermatology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Background:
Destruction of melanocytes mediated by autoimmunity is currently believed as the main cause of vitiligo. This article aims to identify the role of CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) axis in vitiligo and provide new possibilities for the clinical treatment of vitiligo.
Methods:
A total of 30 patients with vitiligo from Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University were recruited based on the inclusion and exclusion criteria. Trephine was used to obtain skin samples from the lesion area and its surrounding normal areas, and the expression levels of CCL17, CCR4, Tbx21, Eomes, and Blimp1 were determined by quantitative reverse transcription polymerase chain reaction. Vitiligo mouse model was established by adoptively transferring CFP-PMEL CD8+ T cells into sublethally irradiated Krt14-Kitl* mice. Recipient mice received intraperitoneal injection of 1 × 106 plaque-forming units of rVV-hPMEL on the same day of transfer. The degree of depigmentation was scored blindly by one observer 5 weeks after vitiligo induction. CFP-PMEL CD8+ T cells migration to skin, draining lymph nodes, spleen, and blood were detected by flow cytometry. CCR4 blockade was performed by intraperitoneal injection of neutralizing antibody.
Results:
The expression levels of CCL17, CCR4, Tbx21, Eomes, and Blimp1 in skin lesions were significantly increased compared with that in surrounding normal areas. CCL17-/- and CCR4-/- mice exhibited significantly lower disease scores than WT mice. The CFP-PMEL CD8+ T cells accumulation was significantly decreased in the skin of CCL17-/- and CCR4-/- mice, but was not changed in draining lymph nodes, spleen, and blood. Administration of CCR4 neutralizing antibody decreased the degree of depigmentation and the recruitment of CFP-PMEL CD8+ T cells to the skin, while keeping the number of T cells in draining lymph nodes unchanged.
Conclusion:
Targeting CCL17-CCR4 axis might inhibit T cell migrating to skin and alleviate vitiligo progression.
Insights
Targeting the CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) axis may inhibit T cell migration to the skin, potentially alleviating vitiligo progression and offering new treatment avenues.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Vitiligo is primarily caused by autoimmune destruction of melanocytes.
- The CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) axis is investigated for its role in vitiligo pathogenesis.
- This study explores novel therapeutic strategies for vitiligo by examining the CCL17-CCR4 pathway.
Purpose of the Study:
- To elucidate the involvement of the CCL17-CCR4 axis in vitiligo.
- To assess the potential of targeting this axis for vitiligo treatment.
- To provide new therapeutic possibilities for vitiligo patients.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure gene expression in human skin samples.
- A vitiligo mouse model was established using adoptive T cell transfer and irradiation.
- CCR4 blockade was performed using a neutralizing antibody in the mouse model.
Main Results:
- CCL17 and CCR4 expression levels were significantly elevated in vitiligo skin lesions compared to normal skin.
- Mice lacking CCL17 or CCR4 showed reduced disease severity and decreased T cell accumulation in the skin.
- CCR4 blockade reduced depigmentation and T cell recruitment to the skin in the mouse model.
Conclusions:
- The CCL17-CCR4 axis plays a crucial role in T cell migration to the skin in vitiligo.
- Targeting the CCL17-CCR4 axis offers a promising therapeutic strategy to inhibit T cell migration and manage vitiligo progression.
