Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease.

Autor: Akama-Garren EH; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.; Harvard-MIT Health Sciences and Technology, Harvard Medical School, Boston, MA, 02115, USA., van den Broek T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Simoni L; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Castrillon C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., van der Poel CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. michael.carroll@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Nov 18; Vol. 12 (1), pp. 6687. Date of Electronic Publication: 2021 Nov 18.
DOI: 10.1038/s41467-021-27035-8
Abstrakt: Pathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease, allowing for analyses of paired transcriptomes and unbiased TCRαβ repertoires at single cell resolution. A minority of clonotypes are preferentially shared amongst autoimmune follicular T cells and clonotypic expansion is associated with differential gene signatures in autoimmune disease. Antigen prediction using algorithmic and machine learning approaches indicates convergence towards shared specificities between non-autoimmune and autoimmune follicular T cells. However, differential autoimmune transcriptional signatures are preserved even amongst follicular T cells with shared predicted specificities. These results demonstrate that follicular T cells are phenotypically distinct in B cell-driven autoimmune disease, providing potential therapeutic targets to modulate autoantibody development.
(© 2021. The Author(s).)
Databáze: MEDLINE
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