Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma

Yoshiaki Yasumizu, Naganari Ohkura (), Hisashi Murata, Makoto Kinoshita, Soichiro Funaki, Satoshi Nojima, Kansuke Kido, Masaharu Kohara, Daisuke Motooka, Daisuke Okuzaki, Shuji Suganami, Eriko Takeuchi, Yamami Nakamura, Yusuke Takeshima, Masaya Arai, Satoru Tada, Meinoshin Okumura, Eiichi Morii, Yasushi Shintani, Shimon Sakaguchi, Tatsusada Okuno () and Hideki Mochizuki
Additional contact information
Yoshiaki Yasumizu: Osaka University
Naganari Ohkura: Osaka University
Hisashi Murata: Osaka University
Makoto Kinoshita: Osaka University
Soichiro Funaki: Osaka University
Satoshi Nojima: Osaka University
Kansuke Kido: Osaka University
Masaharu Kohara: Osaka University
Daisuke Motooka: Osaka University
Daisuke Okuzaki: Osaka University
Shuji Suganami: Osaka University
Eriko Takeuchi: Osaka University
Yamami Nakamura: Osaka University
Yusuke Takeshima: Osaka University
Masaya Arai: Osaka University
Satoru Tada: Osaka University
Meinoshin Okumura: National Hospital Organization Osaka Toneyama Medical Center
Eiichi Morii: Osaka University
Yasushi Shintani: Osaka University
Shimon Sakaguchi: Osaka University
Tatsusada Okuno: Osaka University
Hideki Mochizuki: Osaka University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Myasthenia gravis (MG) is a neurological disease caused by autoantibodies against neuromuscular-associated proteins. While MG frequently develops in thymoma patients, the etiologic factors for MG are not well understood. Here, by constructing a comprehensive atlas of thymoma using bulk and single-cell RNA-sequencing, we identify ectopic expression of neuromuscular molecules in MG-type thymoma. These molecules are found within a distinct subpopulation of medullary thymic epithelial cells (mTECs), which we name neuromuscular mTECs (nmTECs). MG-thymoma also exhibits microenvironments dedicated to autoantibody production, including ectopic germinal center formation, T follicular helper cell accumulation, and type 2 conventional dendritic cell migration. Cell–cell interaction analysis also predicts the interaction between nmTECs and T/B cells via CXCL12-CXCR4. The enrichment of nmTECs presenting neuromuscular molecules within MG-thymoma is further confirmed immunohistochemically and by cellular composition estimation from the MG-thymoma transcriptome. Altogether, this study suggests that nmTECs have a significant function in MG pathogenesis via ectopic expression of neuromuscular molecules.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31951-8

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DOI: 10.1038/s41467-022-31951-8

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