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Single-cell RNA sequencing unveils a unique IL-10-producing T follicular helper subset that sustains humoral immunity during chronic viral infection

ABSTRACT: Single-cell RNA sequencing unveils a unique IL-10-producing T follicular helper subset that sustains humoral immunity during chronic viral infection

PROVIDER: PRJNA435609 | ENA |

REPOSITORIES: ENA

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Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection.

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Single-cell RNA sequencing unveils a unique IL-10-producing T follicular helper subset that sustains humoral immunity during chronic viral infection

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Store-operated Ca2+ entry in follicular T cells controls humoral immune responses and autoimmunity

Project description:T follicular helper (TFH) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (TFR) cells limit GC reaction. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Here we show that SOCE is required for the differentiation and function of both TFH and TFR cells. Conditional deletion of Stim1 and Stim2 genes in T cells or Treg cells results in spontaneous autoantibody production and humoral autoimmunity. Conversely, antibody-mediated immune responses following viral infection critically depend on SOCE in TFH cells. Mechanistically, STIM1 and STIM2 control early TFR and TFH cell differentiation through NFAT-mediated IRF4, BATF and Bcl-6 expression. SOCE plays a dual role in GC response by controlling TFH and TFR cell function, thus enabling protective B cell responses and preventing humoral autoimmunity. RNAseq analyses of WT and Stim1Stim2 DKO follicular T cells and non-follicular T cells; 4-6 mice per cohort in duplicates. Mice were infected for 10 days with LCMV.

2016-03-10 | E-GEOD-79039 | biostudies-arrayexpress

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