Cell Reports (Aug 2023)
SLC38A5 aggravates DC-mediated psoriasiform skin inflammation via potentiating lysosomal acidification
- Leqing Zhu,
- Xichun Xia,
- Guangqiang Li,
- Chuyun Zhu,
- Qingqing Li,
- Baocheng Wang,
- Nan-Xi Shi,
- Zhiwei Lei,
- Shuxian Yang,
- Zhanpeng Zhang,
- Haishan Li,
- Jingyi Tan,
- Zonghua Liu,
- Qiong Wen,
- Hui Zhong,
- Xue-Jia Lin,
- Guodong Sun,
- Xiucong Bao,
- Qian Wang,
- Liehua Deng,
- Lianghua Bin,
- Guangchao Cao,
- Zhinan Yin
Affiliations
- Leqing Zhu
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Department of Dermatology, First Affiliated Hospital, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangzhou National Laboratory, Guangzhou International BioIsland, Guangzhou 510005, China
- Xichun Xia
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China
- Guangqiang Li
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China
- Chuyun Zhu
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China
- Qingqing Li
- Department of Dermatology, Guangdong Women’s and Children’s Hospital, Guangzhou 511442, China
- Baocheng Wang
- Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, China
- Nan-Xi Shi
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China
- Zhiwei Lei
- The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, China; Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China
- Shuxian Yang
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China
- Zhanpeng Zhang
- Department of Dermatology, First Affiliated Hospital, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China
- Haishan Li
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China
- Jingyi Tan
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China
- Zonghua Liu
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China
- Qiong Wen
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China
- Hui Zhong
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China
- Xue-Jia Lin
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China
- Guodong Sun
- Guandgong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People’s Hospital), Jinan University, Heyuan 517000, China
- Xiucong Bao
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Qian Wang
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; Corresponding author
- Liehua Deng
- Department of Dermatology, First Affiliated Hospital, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Corresponding author
- Lianghua Bin
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Corresponding author
- Guangchao Cao
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; Corresponding author
- Zhinan Yin
- The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 8
p. 112910
Abstract
Summary: Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1β from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.
