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BACKGROUND: <p>Alkaline phosphatase (ALP) is a well-established molecular marker of dermal papilla (DP) cells, and its activity closely correlates with their hair-inductive (trichogenic) capacity. This study aimed to identify downstream effectors regulated by ALP that contribute to trichogenicity, and to validate their functional significance in hair follicle neogenesis.</p> METHODS: <p>A cytokine array was employed to screen ALP-dependent secreted factors in three-dimensional (3D) cultured human DP spheres. The expression of C–C motif chemokine ligand 5 (CCL5) and its receptor C–C chemokine receptor type 1 (CCR1) was confirmed by quantitative real-time PCR and immunohistochemistry in human hair follicles and murine skin. Functional roles of CCL5 in DP spheres and CCR1 in mouse epidermal cells were evaluated using siRNA-mediated knockdown followed by <i>in vivo</i> patch hair regeneration assays.</p> RESULTS: <p>ALP knockdown significantly reduced CCL5 expression in DP spheres. Silencing of CCL5 in DP spheres markedly decreased their hair-inductive capacity, while CCR1 knockdown in epidermal cells impaired hair follicle formation. Combined knockdown of CCL5 in DP cells and CCR1 in epidermal cells completely abolished hair follicle neogenesis.</p> CONCLUSION: <p>These findings identify CCL5 as a critical downstream mediator of ALP-regulated trichogenicity in human DP spheres, with CCR1 serving as its essential receptor in epidermal cells. The ALP-CCL5-CCR1 axis represents a promising therapeutic target for promoting hair regeneration.</p>

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Alkaline Phosphatase–Regulated C–C Motif Chemokine Ligand 5 (CCL5) Functions as a Critical Mediator of Hair Follicle Neogenesis

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Mi Hee Kwack,
  • Myungsu Jung,
  • Young Kwan Sung

摘要

BACKGROUND:

Alkaline phosphatase (ALP) is a well-established molecular marker of dermal papilla (DP) cells, and its activity closely correlates with their hair-inductive (trichogenic) capacity. This study aimed to identify downstream effectors regulated by ALP that contribute to trichogenicity, and to validate their functional significance in hair follicle neogenesis.

METHODS:

A cytokine array was employed to screen ALP-dependent secreted factors in three-dimensional (3D) cultured human DP spheres. The expression of C–C motif chemokine ligand 5 (CCL5) and its receptor C–C chemokine receptor type 1 (CCR1) was confirmed by quantitative real-time PCR and immunohistochemistry in human hair follicles and murine skin. Functional roles of CCL5 in DP spheres and CCR1 in mouse epidermal cells were evaluated using siRNA-mediated knockdown followed by in vivo patch hair regeneration assays.

RESULTS:

ALP knockdown significantly reduced CCL5 expression in DP spheres. Silencing of CCL5 in DP spheres markedly decreased their hair-inductive capacity, while CCR1 knockdown in epidermal cells impaired hair follicle formation. Combined knockdown of CCL5 in DP cells and CCR1 in epidermal cells completely abolished hair follicle neogenesis.

CONCLUSION:

These findings identify CCL5 as a critical downstream mediator of ALP-regulated trichogenicity in human DP spheres, with CCR1 serving as its essential receptor in epidermal cells. The ALP-CCL5-CCR1 axis represents a promising therapeutic target for promoting hair regeneration.