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- 조회175
J. Clin. Invest., Published March 11, 2025 | https://doi.org/10.1172/JCI182790
Transcriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis
Jessica Wei1,2*†, Jeonghyeon Moon1,2*, Yoshiaki Yasumizu1,2,3, Le Zhang1, Khadir Radassi1, Nicholas Buitrago-Pocasangre1, M. Elizabeth Deerhake1, Nicolas Strauli4, Chun-Wei Chen4‡, Ann Herman4, Rosetta Pedotti5, Catarina Raposo5, Isaiah Yim6, Jenna Pappalardo1,2¶, Erin E. Longbrake1, Tomokazu S. Sumida1, Pierre-Paul Axisa1,2,7#§, David A. Hafler1,2,8#§
1. Department of Neurology, Yale School of Medicine, New Haven, CT, USA
2. Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
3. Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan
4. Genentech, San Francisco, CA
5. Roche, Basel, Switzerland
6. Department of Biomedical Engineering, Yale University, New Haven, CT, USA
7. Centre de recherches en cancérologie de Toulouse (CRCT), Inserm, Toulouse, France
8. Broad Institute, Boston, MA, USA
*equal contribution
#equal contribution
†present address: Nkarta Inc., San Franscisco, CA, USA
‡present address: Therapeutic Discovery Division, University of Texas MD Anderson Cancer Center, Houston, TX, USA
¶present address: Arcus Biosciences, Hayward, CA, USA
§correspondence: Pierre-Paul Axisa, David A. Hafler
1. Department of Neurology, Yale School of Medicine, New Haven, CT, USA
2. Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
3. Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan
4. Genentech, San Francisco, CA
5. Roche, Basel, Switzerland
6. Department of Biomedical Engineering, Yale University, New Haven, CT, USA
7. Centre de recherches en cancérologie de Toulouse (CRCT), Inserm, Toulouse, France
8. Broad Institute, Boston, MA, USA
*equal contribution
#equal contribution
†present address: Nkarta Inc., San Franscisco, CA, USA
‡present address: Therapeutic Discovery Division, University of Texas MD Anderson Cancer Center, Houston, TX, USA
¶present address: Arcus Biosciences, Hayward, CA, USA
§correspondence: Pierre-Paul Axisa, David A. Hafler
Abstract
Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. While previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic impact on patient immune landscape is unknown. In this study, we explored how B cell depleting therapies modulate the immune landscape using single-cell RNA sequencing (scRNAseq). We demonstrate that B cell depletion leads to cell type-specific changes in the abundance and function of CSF macrophages and peripheral blood monocytes. Specifically, a CSF-specific macrophage population with an anti-inflammatory transcriptomic signature and peripheral CD16+ monocytes increased in frequency post-B cell depletion. This was accompanied by increases in TNFα messenger RNA and protein in monocytes post-B cell depletion, consistent with the finding that anti-TNFα treatment exacerbates autoimmune activity in MS. In parallel, B cell depletion induced changes in peripheral CD4+ T cell populations, including increases in the frequency of TIGIT+ regulatory T cells and marked decreases in the frequency of myelin peptide loaded-tetramer binding CD4+ T cells. Collectively, this study provides an exhaustive transcriptomic map of immunological changes, revealing different cell-type specific reprogramming as a result of B cell depletion treatment in MS.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-12)
- 국외 연구진
- 의약학 > 면역의학
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