The mechano-chemical circuit in fibroblasts and dendritic cells drives basal cell proliferation in psoriasis
Jingwei Jiang,
Xinyi Shao,
Weiwei Liu,
Mengyue Wang,
Qiwei Li,
Miaomiao Wang,
Yang Xiao,
Ke Li,
Huan Liang,
Nian’ou Wang,
Xuegang Xu,
Yan Wu,
Xinghua Gao,
Qiaoli Xie,
Xiao Xiang,
Wanqian Liu,
Wang Wu,
Li Yang,
Zhong-Ze Gu,
Jin Chen,
Mingxing Lei
Affiliations
Jingwei Jiang
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Xinyi Shao
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
Weiwei Liu
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Mengyue Wang
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Qiwei Li
State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
Miaomiao Wang
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Yang Xiao
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Ke Li
Shenzhen Accompany Technology Co., Ltd, Shenzhen 518000, China
Huan Liang
Shenzhen Accompany Technology Co., Ltd, Shenzhen 518000, China
Nian’ou Wang
Shenzhen Accompany Technology Co., Ltd, Shenzhen 518000, China
Xuegang Xu
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, China
Yan Wu
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, China
Xinghua Gao
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, China
Qiaoli Xie
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Xiao Xiang
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Wanqian Liu
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Wang Wu
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China; Corresponding author
Li Yang
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Zhong-Ze Gu
State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
Jin Chen
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China; Corresponding author
Mingxing Lei
Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China; Corresponding author
Summary: Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.
