{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:27:53Z","timestamp":1787740073536,"version":"build-2784847793"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":331,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government Ministry of Science & Information and Communications Technology","award":["NRF-2020R1C1C1005122"],"award-info":[{"award-number":["NRF-2020R1C1C1005122"]}]},{"name":"Medical Scientist Training Program from the Ministry of Science & Information and Communications Technology of Korea"},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare, Republic of Korea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the brain and spinal cord. Despite the crucial role of aberrant immune responses in ALS pathogenesis, studies investigating immunological profiles in the cerebrospinal fluid (CSF) of patients with ALS have reported inconsistent findings. Herein, we explored the intrathecal adaptive immune response and features of circulating T cells between CSF and blood of patients with ALS using single-cell RNA and T-cell receptor (TCR) sequencing. This study comprised a total of 11 patients with apparently sporadic ALS and three controls with non-inflammatory diseases. We collected CSF from all participants, and for three patients with ALS, we additionally obtained paired samples of peripheral blood mononuclear cells (PBMCs). Utilizing droplet-based single-cell RNA and TCR sequencing, we analysed immunological profiles, gene expression characteristics and clonality. Furthermore, we examined T-cell characteristics in both PBMC and CSF samples, evaluating the shared T-cell clones across these compartments. In the CSF, patients with ALS exhibited a lower proportion of CD4+ T cells (45.2 versus 61.2%, P = 0.005) and a higher proportion of CD8+ \u00a0GZMKhi effector memory T cells (TEMs) than controls (21.7 versus 16.8%, P = 0.060). Higher clonality was observed in CD8+ TEMs in patients with ALS compared with controls. In addition, CSF macrophages of patients with ALS exhibited a significant increase in chemokines recruiting CD8+ TEMs. Immunohistochemical analysis showed slightly higher proportions of T cells in the perivascular and parenchymal spaces in patients with ALS than in controls, and CD8+ TEMs co-localized with neurons or astrocytes in the motor cortices of patients with ALS. Clonally expanded CD8+ \u00a0GZMKhi TEMs primarily comprised shared T-cell clones between CSF and PBMCs. Moreover, the shared CD8+ TEMs of PBMCs exhibited gene expression profiles similar to CSF T cells. Patients with ALS showed an increase in proportion and clonality of CD8+ \u00a0GZMKhi TEMs and activated features of macrophages in CSF. The shared T-cell clone between CSF and blood was mainly composed of expanded CD8+ \u00a0GZMKhi TEMs. In conclusion, single-cell immune profiling provided novel insights into the pathogenesis of ALS, characterized by activated macrophages and clonally expanded CD8+ T cells potentially communicating with the central nervous system and peripheral circulation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae428","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T23:25:01Z","timestamp":1732577101000},"source":"Crossref","is-referenced-by-count":14,"title":["Single-cell analysis reveals expanded CD8+ \u00a0\n                    <i>GZMK<\/i>\n                    high T cells in CSF and shared peripheral clones in sporadic amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"6","author":[{"given":"Hyo Jae","family":"Kim","sequence":"first","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon 34141 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Jun","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho","family":"Kang","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon 34141 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Ryeong","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Hi","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Joon","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hye","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon 34141 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Jin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"issue":"10360","key":"2024122016284385200_fcae428-B1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"issue":"12","key":"2024122016284385200_fcae428-B2","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1093\/brain\/awaa309","article-title":"The microglial component of amyotrophic lateral 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