Frontiers in Immunology (Jul 2021)
Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
- Zhili Deng,
- Zhili Deng,
- Zhili Deng,
- Zhili Deng,
- Zhili Deng,
- Fangfen Liu,
- Mengting Chen,
- Mengting Chen,
- Mengting Chen,
- Mengting Chen,
- Mengting Chen,
- Chuchu Huang,
- Chuchu Huang,
- Chuchu Huang,
- Chuchu Huang,
- Chuchu Huang,
- Wenqin Xiao,
- Wenqin Xiao,
- Wenqin Xiao,
- Wenqin Xiao,
- Wenqin Xiao,
- Sini Gao,
- Dan Jian,
- Yuyan Ouyang,
- San Xu,
- San Xu,
- San Xu,
- San Xu,
- San Xu,
- Jinmao Li,
- Qian Shi,
- Hongfu Xie,
- Hongfu Xie,
- Hongfu Xie,
- Hongfu Xie,
- Guohong Zhang,
- Ji Li,
- Ji Li,
- Ji Li,
- Ji Li,
- Ji Li,
- Ji Li
Affiliations
- Zhili Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Zhili Deng
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- Zhili Deng
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- Zhili Deng
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Zhili Deng
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China
- Fangfen Liu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Mengting Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Mengting Chen
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- Mengting Chen
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- Mengting Chen
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Mengting Chen
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China
- Chuchu Huang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Chuchu Huang
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- Chuchu Huang
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- Chuchu Huang
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Chuchu Huang
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China
- Wenqin Xiao
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Wenqin Xiao
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- Wenqin Xiao
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- Wenqin Xiao
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Wenqin Xiao
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China
- Sini Gao
- Department of Pathology, Shantou University Medical College, Shantou, China
- Dan Jian
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Yuyan Ouyang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- San Xu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- San Xu
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- San Xu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- San Xu
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- San Xu
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China
- Jinmao Li
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Qian Shi
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Hongfu Xie
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Hongfu Xie
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- Hongfu Xie
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- Hongfu Xie
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Guohong Zhang
- Department of Pathology, Shantou University Medical College, Shantou, China
- Ji Li
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- Ji Li
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
- Ji Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, China
- Ji Li
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Ji Li
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China
- Ji Li
- Department of Dermatology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- DOI
- https://doi.org/10.3389/fimmu.2021.674871
- Journal volume & issue
-
Vol. 12
Abstract
Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial–immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial–immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea.
Keywords
