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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cellular & molecular immunology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40550921/ |
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| author | Xia, Tian Zhang, Wenlu Wu, Rundong Zhang, Xiaowei Xia, Rongshuang Hu, Xiao Wu, Shuai Liao, Yanhang Li, Jiacheng Liu, Youxi Liu, Yiman Guo, Zhuolin Zhang, Chi Liu, Wenjie Chen, Ming Lu, Jiajing Shi, Yuling Zhang, Ling-Juan |
| author_facet | Xia, Tian Zhang, Wenlu Wu, Rundong Zhang, Xiaowei Xia, Rongshuang Hu, Xiao Wu, Shuai Liao, Yanhang Li, Jiacheng Liu, Youxi Liu, Yiman Guo, Zhuolin Zhang, Chi Liu, Wenjie Chen, Ming Lu, Jiajing Shi, Yuling Zhang, Ling-Juan Xia, Tian Zhang, Wenlu Wu, Rundong Zhang, Xiaowei Xia, Rongshuang Hu, Xiao Wu, Shuai Liao, Yanhang Li, Jiacheng Liu, Youxi Liu, Yiman Guo, Zhuolin Zhang, Chi Liu, Wenjie Chen, Ming Lu, Jiajing Shi, Yuling Zhang, Ling-Juan |
| collection | PubMed - marine biology |
| contents | Dermal adipogenesis protects against neutrophilic skin inflammation during psoriasis pathogenesis. Xia, Tian Zhang, Wenlu Wu, Rundong Zhang, Xiaowei Xia, Rongshuang Hu, Xiao Wu, Shuai Liao, Yanhang Li, Jiacheng Liu, Youxi Liu, Yiman Guo, Zhuolin Zhang, Chi Liu, Wenjie Chen, Ming Lu, Jiajing Shi, Yuling Zhang, Ling-Juan Psoriasis Animals Adipogenesis Neutrophils Mice Humans Skin Inflammation PPAR gamma Adipocytes Dermis Disease Models, Animal Mice, Inbred C57BL Fibroblasts Signal Transduction Adipose Tissue, White Interleukin-1beta The immune response of the skin to danger signals involves rapid recruitment of neutrophils, but their excessive accumulation leads to inflammatory skin diseases, such as psoriasis; however, the mechanisms governing their initiation and resolution are poorly understood. Here, we revealed a dynamic immunoregulatory role of dermal white adipose tissue (dWAT) in the progression and resolution of neutrophilic skin inflammation in an imiquimod-induced psoriasis mouse model. During inflammation onset, dWAT repopulates PDGFRA preadipocytes (pAds), which secrete CXCL1 and SAA3, attracting and activating CXCR2 neutrophils. These neutrophils further activate pAds through the IL-1R-NFκB-C/EBPδ pathway, establishing a self-sustaining inflammatory loop. Paradoxically, prolonged IL-1β signaling triggers PPARγ-dependent adipogenesis, transitioning pAds into anti-inflammatory early adipocytes that resolve neutrophilic inflammation via lipid mediators. Inhibition of adipogenesis, via pharmacological or genetic inhibition of PPARγ, disrupts the formation of early adipocytes, prevents neutrophil regression, and exacerbates inflammation. Analysis of human psoriatic cells revealed a C/EBPδ dermal fibroblast (dFB) subpopulation enriched with preadipocytes, the IL-1 pathway, and inflammatory gene signatures. Furthermore, transcriptomic analyses revealed a negative correlation between the neutrophil-related inflammatory response and the dermal lipogenesis response in generalized pustular psoriasis. Together, our findings reveal the dual role of dWAT: PDGFRA+ pAds initiate inflammation via CXCL1/IL-1β crosstalk with neutrophils, whereas PPARγ-driven adipogenesis resolves this process through lipid mediators. This work establishes dWAT as a critical immunomodulatory hub and proposes adipogenic reprogramming of proinflammatory fibroblasts or topical delivery of early adipocyte lipids as innovative therapies for neutrophil-driven skin diseases, such as psoriasis and ulcers. |
| format | Artículo científico |
| id | pubmed_40550921 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Cellular & molecular immunology |
| record_format | pubmed |
| spellingShingle | Dermal adipogenesis protects against neutrophilic skin inflammation during psoriasis pathogenesis. Xia, Tian Zhang, Wenlu Wu, Rundong Zhang, Xiaowei Xia, Rongshuang Hu, Xiao Wu, Shuai Liao, Yanhang Li, Jiacheng Liu, Youxi Liu, Yiman Guo, Zhuolin Zhang, Chi Liu, Wenjie Chen, Ming Lu, Jiajing Shi, Yuling Zhang, Ling-Juan Psoriasis Animals Adipogenesis Neutrophils Mice Humans Skin Inflammation PPAR gamma Adipocytes Dermis Disease Models, Animal Mice, Inbred C57BL Fibroblasts Signal Transduction Adipose Tissue, White Interleukin-1beta Dermal adipogenesis protects against neutrophilic skin inflammation during psoriasis pathogenesis. Xia, Tian Zhang, Wenlu Wu, Rundong Zhang, Xiaowei Xia, Rongshuang Hu, Xiao Wu, Shuai Liao, Yanhang Li, Jiacheng Liu, Youxi Liu, Yiman Guo, Zhuolin Zhang, Chi Liu, Wenjie Chen, Ming Lu, Jiajing Shi, Yuling Zhang, Ling-Juan Psoriasis Animals Adipogenesis Neutrophils Mice Humans Skin Inflammation PPAR gamma Adipocytes Dermis Disease Models, Animal Mice, Inbred C57BL Fibroblasts Signal Transduction Adipose Tissue, White Interleukin-1beta The immune response of the skin to danger signals involves rapid recruitment of neutrophils, but their excessive accumulation leads to inflammatory skin diseases, such as psoriasis; however, the mechanisms governing their initiation and resolution are poorly understood. Here, we revealed a dynamic immunoregulatory role of dermal white adipose tissue (dWAT) in the progression and resolution of neutrophilic skin inflammation in an imiquimod-induced psoriasis mouse model. During inflammation onset, dWAT repopulates PDGFRA preadipocytes (pAds), which secrete CXCL1 and SAA3, attracting and activating CXCR2 neutrophils. These neutrophils further activate pAds through the IL-1R-NFκB-C/EBPδ pathway, establishing a self-sustaining inflammatory loop. Paradoxically, prolonged IL-1β signaling triggers PPARγ-dependent adipogenesis, transitioning pAds into anti-inflammatory early adipocytes that resolve neutrophilic inflammation via lipid mediators. Inhibition of adipogenesis, via pharmacological or genetic inhibition of PPARγ, disrupts the formation of early adipocytes, prevents neutrophil regression, and exacerbates inflammation. Analysis of human psoriatic cells revealed a C/EBPδ dermal fibroblast (dFB) subpopulation enriched with preadipocytes, the IL-1 pathway, and inflammatory gene signatures. Furthermore, transcriptomic analyses revealed a negative correlation between the neutrophil-related inflammatory response and the dermal lipogenesis response in generalized pustular psoriasis. Together, our findings reveal the dual role of dWAT: PDGFRA+ pAds initiate inflammation via CXCL1/IL-1β crosstalk with neutrophils, whereas PPARγ-driven adipogenesis resolves this process through lipid mediators. This work establishes dWAT as a critical immunomodulatory hub and proposes adipogenic reprogramming of proinflammatory fibroblasts or topical delivery of early adipocyte lipids as innovative therapies for neutrophil-driven skin diseases, such as psoriasis and ulcers. |
| title | Dermal adipogenesis protects against neutrophilic skin inflammation during psoriasis pathogenesis. |
| topic | Psoriasis Animals Adipogenesis Neutrophils Mice Humans Skin Inflammation PPAR gamma Adipocytes Dermis Disease Models, Animal Mice, Inbred C57BL Fibroblasts Signal Transduction Adipose Tissue, White Interleukin-1beta |
| url | https://pubmed.ncbi.nlm.nih.gov/40550921/ |