The elucidation of the thymus-intestinal-vagus nerve-spleen network in systemic lupus erythematosus.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20770
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Shirakashi Mirei 京都大学, 医学研究科, 特定病院助教 (10934367)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 自律神経 / T細胞

Outline of Final Research Achievements

In the HRV results, B6SKG exhibited higher parasympathetic activity compared to B6WT. B6SKG mice underwent vagotomy and were divided into a vagotomized group (Vx) and a sham-operated group (sham), and their phenotypes were evaluated. Immune complex deposition in the glomeruli was weaker in the Vx group, and the increase in anti-dsDNA antibodies was mild. FACS analysis showed a tendency for lower Tfh cells in the Vx group. B6SKG exhibited a slight increase in β2AR expression and a tendency for higher serum NAd levels in the Vx group. The Vx group also showed a decrease in the genus Lactobacillus in the feces of B6SKG, suggesting that the correction of T cell differentiation abnormalities due to TCR signal abnormalities through gut microbiota mediated by the autonomic nervous system contributes to SLE.

Free Research Field

自己免疫疾患

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患への迷走神経刺激術については疼痛や疲労などに対して検討されているが、疾患活動性に対する影響をみたものは多くなかった。今回、腸管の免疫に重要な役割を持つT細胞の伝達異常を背景にもつモデルで迷走神経切断を行ったところ、疾患活動性は改善した。このことは、遺伝的背景に応じて、自律神経に与える影響が異なることを示しており、どのような症例が自律神経に対する介入を行うべきかを検討する必要があることにつながる。今回、迷走神経を切断することで腸内細菌の変容を認めており、表現型も予想とは異なるものになった。胸腺におけるT細胞選択異常が、自律神経を介した腸管免疫にも影響を与えることがわかった。