T cell plasticity in systemic lupus erythematosus revealed by large-scale T cell receptor repertoire and transcriptome studies
Nagafuchi, Y.; Nakano, M.; Lagattuta, K. A.; Ota, M.; Hatano, H.; Takahashi, H.; Itamiya, T.; Inokuchi, H.; Raychaudhuri, S.; Okamura, T.; Fujio, K.; Ishigaki, K.
Show abstract
CD4+ T cell plasticity plays a pivotal role in immune homeostasis. However, evidence of T cell plasticity and its pathological role in human systemic lupus erythematosus (SLE) is missing due to the lack of a reporter system. Here we utilized T cell receptor (TCR) repertoire data as a molecular signatures alongside transcriptomic dataset. Using a large-scale ImmuNexUT database of autoimmune disease patients including 117 SLE cases, we quantified T cell plasticity across 13 fine-grained T cell-types. We analyzed 6,392 samples in total and identified two orthogonal signatures of repertoire and transcriptome, the cell-type and disease signatures, allowing us to investigate CD4+ T cell plasticity comprehensively. Among all possible patterns, the plasticity level was the highest in effector regulatory T cells (eTreg) to Th1 plasticity, which was replicated in an independent cohort. Moreover, eTreg-to-Th1 plasticity positively correlated with SLE disease activity. Our study provides novel evidence that Treg plasticity is involved in SLE pathology.
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