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A New Technique for Quantitative Analysis of Hair Loss in Mice Using Grayscale Analysis
Published on: March 9, 2015
Humanized CXCL12 antibody delays onset and modulates immune response in alopecia areata mice: insights from
Seungchan An1, Mei Zheng2, In Guk Park1
1College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea.
Abstract:
It has been demonstrated that CXCL12 inhibits hair growth via CXCR4, and its neutralizing antibody (Ab) increases hair growth in alopecia areata (AA). However, the molecular mechanisms have not been fully elucidated. In the present study, we further prepared humanized CXCL12 Ab for AA treatment and investigated underlying molecular mechanisms using single-cell RNA sequencing. Subcutaneous injection of humanized CXCL12 Ab significantly delayed AA onset in mice, and dorsal skin was analyzed. T cells and dendritic cells/macrophages were increased in the AA model, but decreased after CXCL12 Ab treatment. Pseudobulk RNA sequencing identified 153 differentially expressed genes that were upregulated in AA model and downregulated after Ab treatment. Gene ontology analysis revealed that immune cell chemotaxis and cellular response to type II interferon were upregulated in AA model but downregulated after Ab treatment. We further identified key immune cell-related genes such as Ifng, Cd8a, Ccr5, Ccl4, Ccl5, and Il21r, which were colocalized with Cxcr4 in T cells and regulated by CXCL12 Ab treatment. Notably, CD8+ T cells were significantly increased and activated via Jak/Stat pathway in the AA model but inactivated after CXCL12 Ab treatment. Collectively, these results indicate that humanized CXCL12 Ab is promising for AA treatment via immune modulatory effects.
Insights
Humanized CXCL12 antibody treatment delays alopecia areata (AA) onset by modulating immune cells. This therapy reduces T cells and macrophages, inactivates CD8+ T cells, and shows promise for AA treatment.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- CXCL12/CXCR4 signaling is implicated in inhibiting hair growth.
- Neutralizing CXCL12 antibodies show potential for treating alopecia areata (AA).
- The precise molecular mechanisms underlying CXCL12 antibody efficacy in AA require further investigation.
Purpose of the Study:
- To develop and evaluate a humanized CXCL12 antibody for AA treatment.
- To elucidate the molecular mechanisms of humanized CXCL12 antibody action in AA using single-cell RNA sequencing.
Main Methods:
- Preparation of humanized CXCL12 antibody.
- Induction of AA model in mice and subcutaneous antibody administration.
- Single-cell and pseudobulk RNA sequencing of dorsal skin.
- Gene ontology analysis and identification of key immune-related genes.
Main Results:
- Humanized CXCL12 antibody significantly delayed AA onset in mice.
- T cells and dendritic cells/macrophages, initially increased in the AA model, decreased after antibody treatment.
- Key immune genes (Ifng, Cd8a, Ccr5, Ccl4, Ccl5, Il21r) in T cells were regulated by the antibody.
- CD8+ T cell activation via the Jak/Stat pathway was suppressed by the antibody treatment.
Conclusions:
- Humanized CXCL12 antibody demonstrates therapeutic potential for alopecia areata.
- The antibody exerts its effects through immune modulation, specifically targeting T cell and macrophage populations.
- This study provides mechanistic insights into CXCL12-targeted therapy for AA.
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