Inhibition of Th2 differentiation accelerates chronic wound healing by facilitating lymphangiogenesis Journal Article
| Authors: | Pollack, B. L.; Torrisi, J. S.; Hespe, G. E.; Ashokan, G.; Shin, J.; Mehrara, B. J.; Kataru, R. P. |
| Article Title: | Inhibition of Th2 differentiation accelerates chronic wound healing by facilitating lymphangiogenesis |
| Abstract: | Background/Objectives: Chronic wounds pose a significant healthcare burden, and there remains no effective animal model for study. We aimed to develop a mouse model of chronic wounds that remain open for at least 4 weeks and to investigate the role of the lymphatic system in wound healing. Methods: Full-thickness excisional wounds were created on the dorsal surface of mouse tails to simulate chronic wounds. Lymphatic drainage was assessed using FITC-dextran lymphangiography. Histology and immunofluorescence were used to analyze immune cell infiltration. The effect of inhibiting Th2 differentiation via IL-4 and IL-13 neutralization on wound closure was also evaluated. Results: Our chronic wound model was successful, and wounds remained open for 4 weeks. Impaired lymphatic drainage was observed extending beyond the wound area. Increased CD4+ T-helper cell infiltration and Th2 cell accumulation were observed in the impaired lymphatic drainage zone. Inhibition of IL-4 and IL-13 accelerated wound healing. Conclusions: Impaired lymphatic drainage and Th2-mediated inflammation contribute to delayed healing, and gradients of lymphatic fluid flow are associated with spatial differences in lymphangiogenesis. Targeting Th2 cytokines may offer a novel therapeutic approach for chronic wounds. |
| Keywords: | radiation; inflammation; angiogenesis; lymphangiogenesis; lymphedema; skin; wound healing; fibrosis; lymphatic regeneration; drug-delivery; dysfunction; lymphatics; transport; th2 inflammation; chronic wounds; lecs; rabbit ear model |
| Journal Title: | Biomedicines |
| Volume: | 13 |
| Issue: | 5 |
| ISSN: | 2227-9059 |
| Publisher: | MDPI |
| Date Published: | 2025-05-01 |
| Language: | English |
| ACCESSION: | WOS:001497658500001 |
| DOI: | 10.3390/biomedicines13051026 |
| PROVIDER: | wos |
| PMCID: | PMC12109103 |
| PUBMED: | 40426856 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Raghu P. Kataru -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work