Dataset Information

FACS-sorted CD103+ and CD103- Treg cell proteomics

ABSTRACT: Regulatory T cells (Tregs) play a key role in suppressing systemic effector immune responses, thereby preventing autoimmune diseases but could also potentially contribute to tumor progression. As a result, there is significant interest in the clinical manipulation of Tregs. However, the mechanisms governing induced Treg (iTreg) differentiation are not fully understood. In the present study, we phenotypically profiled human iTregs during early stages of in vitro differentiation at single-cell level using multiparametric mass cytometry. A panel of 25 metal-conjugated antibodies specific to a range of markers associated with human Tregs was used to characterize these immunomodulatory cells. We found that iTregs highly express the transcription factor Foxp3 and characteristic Treg-associated surface markers (e.g. CD25, PD1, CD137, CCR4, CCR7, CXCR3, and CD103). Expression of co-inhibitory factors (e.g. TIM3, LAG3, and TIGIT) increased slightly at late stages of iTreg differentiation. Further, CD103 was selectively upregulated in the iTreg compartment while negatively regulated by Foxp3. Overall, our study highlights that during early stages of differentiation, iTregs resemble memory-like Treg features, and opens possibilities for studying molecular mechanisms of Treg function.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Blood

SUBMITTER: Kedar Batkulwar

LAB HEAD: Riitta Lahesmaa

PROVIDER: PXD052626 | Pride | 2025-05-07

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20240524_124127_240523_CD103_Treg_proteomics.sne	Other
	240523_CD103_NEG_Pool_1.htrms	Other
	240523_CD103_NEG_Pool_1.raw	Raw
	240523_CD103_NEG_Pool_2.htrms	Other
	240523_CD103_NEG_Pool_2.raw	Raw

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Publications

Phenotypic profiling of human induced regulatory T cells at early differentiation: insights into distinct immunosuppressive potential.

Kattelus Roosa R Starskaia Inna I Lindén Markus M Batkulwar Kedar K Pietilä Sami S Moulder Robert R Marson Alexander A Rasool Omid O Suomi Tomi T Elo Laura L LL Lahesmaa Riitta R Buchacher Tanja T

Cellular and molecular life sciences : CMLS 20240912 1

Regulatory T cells (Tregs) play a key role in suppressing systemic effector immune responses, thereby preventing autoimmune diseases but also potentially contributing to tumor progression. Thus, there is great interest in clinically manipulating Tregs, but the precise mechanisms governing in vitro-induced Treg (iTreg) differentiation are not yet fully understood. Here, we used multiparametric mass cytometry to phenotypically profile human iTregs during the early stages of in vitro differentiatio ...[more]

PMID: 39264416

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Project description:Treg dysfunction is associated with a variety of inflammatory diseases. Treg populations are defined by expression of the oligomeric transcription factor FOXP3 and inability to produce IL-2, a cytokine required for T cell maintenance and survival. FOXP3 activity is regulated post-translationally by histone/protein acetyltransferases and histone/protein deacetylases (HDACs). Here, we determined that HDAC3 mediates both the development and function of the two main Treg subsets, thymus-derived Tregs and induced Tregs (iTregs). We determined that HDAC3 and FOXP3 physically interact and that HDAC3 expression markedly reduces Il2 promoter activity. In murine models, conditional deletion of Hdac3 during thymic Treg development restored Treg production of IL-2 and blocked the suppressive function of Tregs. HDAC3-deficient mice died from autoimmunity by 4-6 weeks of age; however, injection of WT FOXP3+ Tregs prolonged survival. Adoptive transfer of Hdac3-deficient Tregs, unlike WT Tregs, did not control T cell proliferation in naive mice and did not prevent allograft rejection or colitis. HDAC3 also regulated the development of iTregs, as HDAC3-deficient conventional T cells were not converted into iTregs under polarizing conditions and produced large amounts of IL-2, IL-6, and IL-17. We conclude that HDAC3 is essential for the normal development and suppressive functions of thymic and peripheral FOXP3+ Tregs. RNA was isolated using RNeasy kits (QIAGEN), and RNA integrity and quantity were analyzed by NanoDrop ND-1000 and Nanochip 2100 Bioanalyzer (Agilent Technologies). Microarray experiments were performed using whole mouse genome oligoarrays (Mouse430a, Affymetrix) and array data analyzed using MAYDAY 2.12 software. Array data were subjected to robust multiarray average (RMA) normalization and analyzed using Student’s t test. Only data with a false discovery rate-adjusted P value of less than 0.05 and at least 2× differential expression were included in the analysis. Data underwent z-score transformation for display.