Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid
Abstract Bullous pemphigoid (BP) triggers profound functional changes in both immune and non-immune cells in the skin and circulation, though the underlying mechanisms remain unclear. In this study, we conduct single-cell transcriptome analysis of lesional and non-lesional skin, as well as blood sam...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07629-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861748123303936 |
|---|---|
| author | Guirong Liang Chenjing Zhao Qin Wei Suying Feng Yetao Wang |
| author_facet | Guirong Liang Chenjing Zhao Qin Wei Suying Feng Yetao Wang |
| author_sort | Guirong Liang |
| collection | DOAJ |
| description | Abstract Bullous pemphigoid (BP) triggers profound functional changes in both immune and non-immune cells in the skin and circulation, though the underlying mechanisms remain unclear. In this study, we conduct single-cell transcriptome analysis of lesional and non-lesional skin, as well as blood samples from BP patients. In lesional skin, non-immune cells upregulate pathways related to metabolism, wound healing, immune activation, and cell migration. LAMP3+DCs from cDC2 show stronger pro-inflammatory signatures than those from cDC1, and VEGFA+ mast cells, crucial for BP progression, are predominantly in lesional skin. As BP patients transition from active to remission stages, blood B cell function shifts from differentiation and memory formation to increased type 1 interferon signaling and reduced IL-4 response. Blood CX3CR1+ ZNF683+ and LAG3+ exhausted T cells exhibit the highest TCR expansion among clones shared with skin CD8+T cells, suggesting their role in fueling skin CD8+T cell clonal expansion. Clinical BP severity correlates positively with blood NK cell IFN-γ production and negatively with amphiregulin (AREG) production. NK cell-derived AREG mitigates IFN-γ-induced keratinocyte apoptosis, suggesting a crucial balance between AREG and IFN-γ in BP progression. These findings highlight functional shifts in BP pathology and suggest potential therapeutic targets. |
| format | Article |
| id | doaj-art-a6b681dea1fd4816b7770166f5023b78 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-a6b681dea1fd4816b7770166f5023b782025-02-09T12:50:50ZengNature PortfolioCommunications Biology2399-36422025-02-018111610.1038/s42003-025-07629-4Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoidGuirong Liang0Chenjing Zhao1Qin Wei2Suying Feng3Yetao Wang4Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Bullous pemphigoid (BP) triggers profound functional changes in both immune and non-immune cells in the skin and circulation, though the underlying mechanisms remain unclear. In this study, we conduct single-cell transcriptome analysis of lesional and non-lesional skin, as well as blood samples from BP patients. In lesional skin, non-immune cells upregulate pathways related to metabolism, wound healing, immune activation, and cell migration. LAMP3+DCs from cDC2 show stronger pro-inflammatory signatures than those from cDC1, and VEGFA+ mast cells, crucial for BP progression, are predominantly in lesional skin. As BP patients transition from active to remission stages, blood B cell function shifts from differentiation and memory formation to increased type 1 interferon signaling and reduced IL-4 response. Blood CX3CR1+ ZNF683+ and LAG3+ exhausted T cells exhibit the highest TCR expansion among clones shared with skin CD8+T cells, suggesting their role in fueling skin CD8+T cell clonal expansion. Clinical BP severity correlates positively with blood NK cell IFN-γ production and negatively with amphiregulin (AREG) production. NK cell-derived AREG mitigates IFN-γ-induced keratinocyte apoptosis, suggesting a crucial balance between AREG and IFN-γ in BP progression. These findings highlight functional shifts in BP pathology and suggest potential therapeutic targets.https://doi.org/10.1038/s42003-025-07629-4 |
| spellingShingle | Guirong Liang Chenjing Zhao Qin Wei Suying Feng Yetao Wang Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid Communications Biology |
| title | Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid |
| title_full | Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid |
| title_fullStr | Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid |
| title_full_unstemmed | Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid |
| title_short | Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid |
| title_sort | single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid |
| url | https://doi.org/10.1038/s42003-025-07629-4 |
| work_keys_str_mv | AT guirongliang singlecelltranscriptomeprofilingrevealspathogenesisofbullouspemphigoid AT chenjingzhao singlecelltranscriptomeprofilingrevealspathogenesisofbullouspemphigoid AT qinwei singlecelltranscriptomeprofilingrevealspathogenesisofbullouspemphigoid AT suyingfeng singlecelltranscriptomeprofilingrevealspathogenesisofbullouspemphigoid AT yetaowang singlecelltranscriptomeprofilingrevealspathogenesisofbullouspemphigoid |