PMID- 37414380 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231106 IS - 1521-7035 (Electronic) IS - 1521-6616 (Linking) VI - 253 DP - 2023 Aug TI - AXL(+)SIGLEC6(+) dendritic cells in cerebrospinal fluid and brain tissues of patients with autoimmune inflammatory demyelinating disease of CNS. PG - 109686 LID - S1521-6616(23)00449-7 [pii] LID - 10.1016/j.clim.2023.109686 [doi] AB - Inflammatory demyelinating disease of the CNS (IDD) is a heterogeneous group of autoimmune diseases, and multiple sclerosis is the most common type. Dendritic cells (DCs), major antigen-presenting cells, have been proposed to play a central role in the pathogenesis of IDD. The AXL(+)SIGLEC6(+) DC (ASDC) has been only recently identified in humans and has a high capability of T cell activation. Nevertheless, its contribution to CNS autoimmunity remains still obscure. Here, we aimed to identify the ASDC in diverse sample types from IDD patients and experimental autoimmune encephalomyelitis (EAE). A detailed analysis of DC subpopulations using single-cell transcriptomics for the paired cerebrospinal fluid (CSF) and blood samples of IDD patients (total n = 9) revealed that three subtypes of DCs (ASDCs, ACY3(+) DCs, and LAMP3(+) DCs) were overrepresented in CSF compared with their paired blood. Among these DCs, ASDCs were also more abundant in CSF of IDD patients than in controls, manifesting poly-adhesional and stimulatory characteristics. In the brain biopsied tissues of IDD patients, obtained at the acute attack of disease, ASDC were also frequently found in close contact with T cells. Lastly, the frequency of ASDC was found to be temporally more abundant in acute attack of disease both in CSF samples of IDD patients and in tissues of EAE, an animal model for CNS autoimmunity. Our analysis suggests that the ASDC might be involved in the pathogenesis of CNS autoimmunity. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Kang, Junho AU - Kang J AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. FAU - Kim, Moonhang AU - Kim M AD - Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Yoon, Da-Young AU - Yoon DY AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Woo-Seok AU - Kim WS AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. FAU - Choi, Seok-Jin AU - Choi SJ AD - Department of Neurology, Seoul National University Hospital, Seoul National University of Medicine, Seoul, Republic of Korea. FAU - Kwon, Young-Nam AU - Kwon YN AD - Department of Neurology, Seoul National University Hospital, Seoul National University of Medicine, Seoul, Republic of Korea. FAU - Kim, Won-Seok AU - Kim WS AD - Department of Neurology, Seoul National University Hospital, Seoul National University of Medicine, Seoul, Republic of Korea. FAU - Park, Sung-Hye AU - Park SH AD - Department of Pathology, Seoul National University Hospital, Seoul National University of Medicine, Seoul, Republic of Korea. FAU - Sung, Jung-Joon AU - Sung JJ AD - Department of Neurology, Seoul National University Hospital, Seoul National University of Medicine, Seoul, Republic of Korea. FAU - Park, Myungsun AU - Park M AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. FAU - Lee, Jung Seok AU - Lee JS AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. FAU - Park, Jong-Eun AU - Park JE AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address: jp24@kaist.ac.kr. FAU - Kim, Sung-Min AU - Kim SM AD - Department of Neurology, Seoul National University Hospital, Seoul National University of Medicine, Seoul, Republic of Korea. Electronic address: sueh916@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230704 PL - United States TA - Clin Immunol JT - Clinical immunology (Orlando, Fla.) JID - 100883537 RN - 0 (SIGLEC6 protein, human) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (Antigens, CD) RN - 0 (Lectins) SB - IM MH - Animals MH - Humans MH - *Encephalomyelitis, Autoimmune, Experimental MH - *Multiple Sclerosis MH - T-Lymphocytes MH - Brain/pathology MH - Dendritic Cells MH - Antigens, Differentiation, Myelomonocytic MH - Antigens, CD MH - Lectins OTO - NOTNLM OT - AXL(+)SIGLEC6(+) dendritic cell OT - Inflammatory demyelinating disease OT - Single-cell RNA sequencing COIS- Declaration of Competing Interest S.M.K has lectured, consulted, and received honoraria from Bayer Schering Pharma, Genzyme, Merck Serono, and UCB; received a grant from the National Research Foundation of Korea and the Korea Health Industry Development Institute Research; is an Associate Editor of the Journal of Clinical Neurology. S.M.K and Seoul National University Hospital have transferred the technology of flow cytometric autoantibody assay to EONE Laboratory, Korea. The remaining authors declare no competing interests. EDAT- 2023/07/07 01:05 MHDA- 2023/10/23 00:44 CRDT- 2023/07/06 19:29 PHST- 2023/03/19 00:00 [received] PHST- 2023/05/26 00:00 [revised] PHST- 2023/06/12 00:00 [accepted] PHST- 2023/10/23 00:44 [medline] PHST- 2023/07/07 01:05 [pubmed] PHST- 2023/07/06 19:29 [entrez] AID - S1521-6616(23)00449-7 [pii] AID - 10.1016/j.clim.2023.109686 [doi] PST - ppublish SO - Clin Immunol. 2023 Aug;253:109686. doi: 10.1016/j.clim.2023.109686. Epub 2023 Jul 4.