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CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and Alopecia Areata

Authors
 Mei Zheng  ;  Min-Ho Kim  ;  Sang-Gyu Park  ;  Won-Serk Kim  ;  Sang-Ho Oh  ;  Jong-Hyuk Sung 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.25(3) : 1705, 2024-01 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2024-01
MeSH
Alopecia / metabolism ; Alopecia Areata* / drug therapy ; Alopecia Areata* / metabolism ; Androgens / metabolism ; Animals ; Antibodies, Neutralizing* / metabolism ; Antibodies, Neutralizing* / pharmacology ; Chemokine CXCL12 / immunology ; Hair ; Hair Follicle / metabolism ; Mice ; Skin / metabolism
Keywords
CXCL12 ; alopecia areata ; androgenic alopecia ; dermal fibroblasts ; neutralizing antibody
Abstract
We had previously investigated the expression and functional role of C-X-C Motif Chemokine Ligand 12 (CXCL12) during the hair cycle progression. CXCL12 was highly expressed in stromal cells such as dermal fibroblasts (DFs) and inhibition of CXCL12 increased hair growth. Therefore, we further investigated whether a CXCL12 neutralizing antibody (αCXCL12) is effective for androgenic alopecia (AGA) and alopecia areata (AA) and studied the underlying molecular mechanism for treating these diseases. In the AGA model, CXCL12 is highly expressed in DFs. Subcutaneous (s.c.) injection of αCXCL12 significantly induced hair growth in AGA mice, and treatment with αCXCL12 attenuated the androgen-induced hair damage in hair organ culture. Androgens increased the secretion of CXCL12 from DFs through the androgen receptor (AR). Secreted CXCL12 from DFs increased the expression of the AR and C-X-C Motif Chemokine Receptor 4 (CXCR4) in dermal papilla cells (DPCs), which induced hair loss in AGA. Likewise, CXCL12 expression is increased in AA mice, while s.c. injection of αCXCL12 significantly inhibited hair loss in AA mice and reduced the number of CD8+, MHC-I+, and MHC-II+ cells in the skin. In addition, injection of αCXCL12 also prevented the onset of AA and reduced the number of CD8+ cells. Interferon-γ (IFNγ) treatment increased the secretion of CXCL12 from DFs through the signal transducer and activator of transcription 3 (STAT3) pathway, and αCXCL12 treatment protected the hair follicle from IFNγ in hair organ culture. Collectively, these results indicate that CXCL12 is involved in the progression of AGA and AA and antibody therapy for CXCL12 is promising for hair loss treatment.
Files in This Item:
T202402320.pdf Download
DOI
10.3390/ijms25031705
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Oh, Sang Ho(오상호) ORCID logo https://orcid.org/0000-0002-4477-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/199093
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