Dataset Information

Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4+ regulatory T cells

ABSTRACT: The CD4+ regulatory T (Treg) cell lineage comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. As a model for Treg cells, studies employ TGF-β-induced (i)Treg cells generated from CD4+ conventional T (Tconv) cells in vitro. Here, we describe the relationship of iTreg cells to tTreg and Tconv cells. Proteomic analysis revealed that iTreg, tTreg and Tconv cell populations each have a unique protein expression pattern. iTreg cells had very limited overlap in protein expression with tTreg cells, regardless of cell activation status and instead shared signaling and metabolic proteins with Tconv cells. tTreg cells had a uniquely modest response to CD3/CD28-mediated stimulation. As a benchmark, we used a previously defined proteomic signature that sets ex vivo naïve and effector phenotype Treg cells apart from Tconv cells and includes unique Treg cell properties (Cuadrado et al., Immunity, 2018). This Treg cell core signature was largely absent in iTreg cells. We also used a proteomic signature that distinguishes ex vivo effector Treg cells from Tconv cells and naïve Treg cells. This effector Treg cell signature was partially present in iTreg cells. In conclusion, iTreg cells are distinct from tTreg cells and share limited features with ex vivo Treg cells at the proteomic level.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Blood

SUBMITTER: Mark Mensink

LAB HEAD: Jannie Borst

PROVIDER: PXD038302 | Pride | 2022-11-28

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20_S13_iTreg_unstimulated.raw	Raw
	21_S13_iTreg_stimulated_rerun.raw	Raw
	26_S15_iTreg_unstimulated.raw	Raw
	27_S15_iTreg_stimulated.raw	Raw
	32_S9b_iTreg_unstimulated.raw	Raw

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Publications

Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4+ regulatory T cells.

Mensink Mark M Schrama Ellen E Cuadrado Eloy E Amsen Derk D de Kivit Sander S Borst Jannie J

Scientific reports 20221124 1

The CD4+ regulatory T (Treg) cell lineage, defined by FOXP3 expression, comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. As a model for Treg cells, studies employ TGF-β-induced (i)Treg cells generated from CD4+ conventional T (Tconv) cells in vitro. Here, we describe how human iTreg cells relate to human blood-derived tTreg and Tconv cells according to proteomic analysis. Each of these cell populations had a unique protein expression pattern. i ...[more]

PMID: 36434024

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Project description:The relative contribution of induced and natural Foxp3+ regulatory T cells (iTreg and nTreg cells, respectively) to the maintenance of tolerance is unknown. We examined their respective roles by in vivo adoptive transfer immunotherapy of newborn Foxp3-deficient BALB/c mice. Survival, weight gain, tissue infiltration, T cell activation, and the concentration of proinflammatory cytokines were used as outcome measurements. Treatment with iTreg cells alone was not successful. While effective in preventing death, treatment with nTreg cells alone was associated with chronic inflammation and autoimmunity. Outcomes markedly improved when conventional T (Tconv) cells were transferred together with the nTreg cells, where 10% of the peripheral Treg cell pool was derived by in-situ conversion. This enhancement depended upon the capacity of Tconv cells to express Foxp3. The gene expression profile of in vivo derived iTreg cells was similar to the established nTreg cell genetic signature. These results identify iTreg cells as an essential regulatory subset that supplements tolerance maintained by nTreg cells. Purified cells sorted by flow cytometry from 4-8 treated mice(pooled EGFP+ Thy1.1+ iTreg cells with that of EGFP+ Thy1.1+ nTreg cells sorted from the spleens and lymph nodes of treated mice) were used to generate total RNA for each iTreg and nTreg array set, which was labeled and hybridized to Affymetrix 430 2.0 GeneChips in accordance to the manufacturer’s protocol. Three sets of arrays were performed, and the results were averaged. Both iTreg and nTreg array sets were compared to a) naïve CD4+EGFP– Tconv cells from Foxp3EGFP mice and b) in vitro derived iTreg cells 72 hours after Foxp3 induction, generated earlier. The subset of probe sets whose expression increased or decreased by twofold or more relative to Tconv cells as a common standard was identified and used for further analysis. Naïve CD4+EGFP– Tconv cells from Foxp3EGFP mice and in vitro derived iTreg cells 72 hours after Foxp3 induction datasets obtained from GSE14415: Naïve CD4+EGFP– Tconv cells from Foxp3EGFP mice: GSM360171 - GSM360173 In vitro derived iTreg cells 72 hours after Foxp3 induction: GSM360147 - GSM360151

Dataset Information

Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4+ regulatory T cells

Dataset's files

Publications

Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4<sup>+</sup> regulatory T cells.

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