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Single-Cell RNA Sequencing of Thymic KN6 γδ T-Cells Modulated by TCR Signal Strength and Notch Signaling

ABSTRACT: γδ T-cells form an integral arm of the immune system through their rapid and potent effector functions, and are critical players during both protective and destructive immunity. However, the factors that dictate γδ T-cell functional programming in vivo remain to be fully elucidated. Here, we employed RBPJ-inducible and KN6-transgenic mice to assess the roles of ontogenic timing, T-cell receptor (TCR) signal strength, and Notch signaling in the generation of γδ T-cell functional subsets in vivo. We found skewed generation of Vγ1+ cells toward the PLZF+ γδ T-cell lineage at the fetal stage. Similarly, generation of interleukin (IL)-17 producing γδ T-cells was favored during, although not exclusive to, the fetal stage. Strong TCR signals, in conjunction with Notch, were necessary for the generation of IL-4 producing γδ T-cells. Conversely, weak TCR signals were amenable for the generation of IL-17 producing γδ T-cells, which was Notch-independent. Additionally and surprisingly, Notch signaling was also dispensable for peripheral γδ T-cell IL-17 production. Thus, our results precisely defined the roles of ontogenic timing, TCR signal strength, and Notch signaling in γδ T-cell functional programming in vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE165908 | GEO | 2021/05/01

REPOSITORIES: GEO

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RNA Sequencing of Fetal and Adult Mature Thymic Vγ1+ γδ T-Cells

Project description:γδ T-cells form an integral arm of the immune system through their rapid and potent effector functions, and are critical players during both protective and destructive immunity. However, the factors that dictate γδ T-cell functional programming in vivo remain to be fully elucidated. Here, we employed RBPJ-inducible and KN6-transgenic mice to assess the roles of ontogenic timing, T-cell receptor (TCR) signal strength, and Notch signaling in the generation of γδ T-cell functional subsets in vivo. We found skewed generation of Vγ1+ cells toward the PLZF+ γδ T-cell lineage at the fetal stage. Similarly, generation of interleukin (IL)-17 producing γδ T-cells was favored during, although not exclusive to, the fetal stage. Strong TCR signals, in conjunction with Notch, were necessary for the generation of IL-4 producing γδ T-cells. Conversely, weak TCR signals were amenable for the generation of IL-17 producing γδ T-cells, which was Notch-independent. Additionally and surprisingly, Notch signaling was also dispensable for peripheral γδ T-cell IL-17 production. Thus, our results precisely defined the roles of ontogenic timing, TCR signal strength, and Notch signaling in γδ T-cell functional programming in vivo.

2021-05-01 | GSE166086 | GEO

TCR signal strength controls thymic differentiation of discrete proinflammatory γδT cell subsetsistinct TCR signal strength requirements in the thymus

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2019-05-22 | E-MTAB-7178 | biostudies-arrayexpress

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Project description:The murine thymus produces discrete Î³Î´ T cell subsets making either IFN-Î³ or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on Î³Î´ T cells. Mice haploinsufficient for both CD3Î³ and CD3Î´ (CD3DH) showed normal Î±Î² thymocyte subsets but specific defects in Î³Î´ T cell development, namely impaired differentiation of IL-17-producing embryonic VÎ³6+ (but not adult VÎ³4+) Î³Î´ T cells and a marked depletion of IFN-Î³-producing CD122+ NK1.1+ (VÎ³1-biased) Î³Î´ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-Î³ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct VÎ³ usage and differential cytokine production by effector Î³Î´ T cell subsets. We investigated the transcriptional changes associated with reduced TCRÎ³Î´ signaling in the CD3DH model. Transcriptome-wide analysis of FACS-purified CD3DH or WT Î³Î´ thymocytes from E18 or 6-week was carried looking for patterns of gene expression during ontogeny

2016-03-29 | E-GEOD-71637 | biostudies-arrayexpress

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2019-10-16 | PXD007574 | Pride

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2018-05-18 | GSE114594 | GEO

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70 [RNA-Seq]

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