PA28γ induces dendritic cell maturation and activates T‐cell immune responses in oral lichen planus
Yimei Wang,
Qiyue Zhang,
Xiaoting Deng,
Ying Wang,
Xin Tian,
Shiyu Zhang,
Yingqiang Shen,
Xikun Zhou,
Xin Zeng,
Qianming Chen,
Lu Jiang,
Jing Li
Affiliations
Yimei Wang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Qiyue Zhang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Xiaoting Deng
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Ying Wang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Xin Tian
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Shiyu Zhang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Yingqiang Shen
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Xikun Zhou
State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu PR China
Xin Zeng
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Qianming Chen
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Lu Jiang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Jing Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology Sichuan University Chengdu Sichuan PR China
Abstract Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune‐related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear. Here, we demonstrated that PA28γ is overexpressed in epithelial cells and inflammatory cells of OLP tissues but has no significant relationship with OLP subtypes. Functionally, keratinocytes with high PA28γ expression could induce dendritic cell (DC) maturation and promote the T‐cell differentiation into Th1 cells in response to the immune response. In addition, we found that a high level of PA28γ expression is associated with high numbers of infiltrating mature DCs and activated T‐cells in OLP tissues. Mechanistically, keratinocytes with high PA28γ expression could promote the secretion of C–C motif chemokine (CCL)5, blocking CCL5 or/and its receptor CD44 could inhibit the induction of T‐cell differentiation by keratinocytes with high PA28γ expression. In conclusion, we reveal that keratinocytes with high expression of PA28γ in OLP can induce DC maturation and promote T‐cell differentiation through the CCL5‐CD44 pathway, providing previously unidentified mechanistic insights into the mechanism of inflammatory progression in OLP.
