Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma
Yoshiaki Yasumizu,
Makoto Kinoshita,
Martin Jinye Zhang,
Daisuke Motooka,
Koichiro Suzuki,
Satoshi Nojima,
Naoshi Koizumi,
Daisuke Okuzaki,
Soichiro Funaki,
Yasushi Shintani,
Naganari Ohkura,
Eiichi Morii,
Tatsusada Okuno,
Hideki Mochizuki
Affiliations
Yoshiaki Yasumizu
Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan; Department of Neurology, Yale School of Medicine, New Haven, CT, USA; Corresponding author
Makoto Kinoshita
Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Martin Jinye Zhang
Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Daisuke Motooka
Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Koichiro Suzuki
BIKEN-RIMD NGS Laboratory, Research Institute for Microbial Diseases, Osaka University, Suita, Japan; Biomedical Science Center, The Research Foundation for Microbial Diseases of Osaka University (BIKEN), Suita, Japan
Satoshi Nojima
Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Naoshi Koizumi
Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Daisuke Okuzaki
Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Soichiro Funaki
Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Yasushi Shintani
Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Naganari Ohkura
Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Department of Frontier Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Eiichi Morii
Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Tatsusada Okuno
Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; Corresponding author
Hideki Mochizuki
Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan
Summary: Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory T cells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research.
