A wave of Thetis cells imparts tolerance to food antigens early in life
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1247582 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33008929.fastq.gz | Fastqsanger.gz | |||
| SRR33008930.fastq.gz | Fastqsanger.gz | |||
| SRR33008931.fastq.gz | Fastqsanger.gz | |||
| SRR33008932.fastq.gz | Fastqsanger.gz | |||
| SRR33008933.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:In the intestine, peripherally induced regulatory T (pTreg) cells play an essential role in suppressing inflammatory responses to food proteins. However, the identity of the antigen-presenting cells that instruct food-specific pTreg cells is poorly understood. We found that a subset of Thetis cells, TC IV, is required for food-specific pTreg cell differentiation. TC IV were almost exclusively present within mesenteric lymph nodes, suggesting that their presence underlies the phenomenon of oral tolerance. A wave of TC IV differentiation in the periweaning period was associated with a window of opportunity for enhanced pTreg cell generation in response to food antigens. Our findings indicate that TC IV may represent a therapeutic target for the treatment of food-associated allergic and inflammatory diseases.
2025-05-01 | GSE294005 | GEO
Project description:Tolerance to self- or innocuous foreign antigens is vital for preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing AutoImmune Regulator, Aire, play a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development. A second wave of Treg cell differentiation occurs in the periphery, upon exposure to dietary and commensal microbiota derived antigens within the first few weeks of life, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells are not known. Here we identified a new lineage of tolerogenic RORγt+ antigen-presenting cells (APC) with a hybrid dendritic cell (DC)-mTEC phenotype, dubbed Thetis cells (TCs), comprising 4 major sub-groups (TC I-IV), We uncovered a developmental wave of TCs within intestinal lymph nodes during a critical early life window, coincident with the wave of pTreg cell differentiation. While Aire+ TC I and III bore remarkable homology with Aire+ mTECs, including expression of tissue restricted self-antigens, TC IV lacked Aire expression and were enriched for molecules required for pTreg generation, including the TGF-β activating integrin αvβ8. Loss of either MHCII or Itgb8 expression by TCs led to a profound impairment in intestinal pTreg differentiation, with onset of intestinal inflammation. In contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical DCs was neither sufficient nor required for pTreg generation, further implicating TCs as the critical tolerogenic RORγt+ APC. Our studies reveal parallel pathways for establishment of tolerance to self and foreign antigen within the thymus and periphery, marked by involvement of shared cellular and transcriptional programs.
2022-09-06 | GSE174405 | GEO
Project description:Tolerance to self- or innocuous foreign antigens is vital for preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing AutoImmune Regulator, Aire, play a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development. A second wave of Treg cell differentiation occurs in the periphery, upon exposure to dietary and commensal microbiota derived antigens within the first few weeks of life, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells are not known. Here we identified a new lineage of tolerogenic RORγt+ antigen-presenting cells (APC) with a hybrid dendritic cell (DC)-mTEC phenotype, dubbed Thetis cells (TCs), comprising 4 major sub-groups (TC I-IV), We uncovered a developmental wave of TCs within intestinal lymph nodes during a critical early life window, coincident with the wave of pTreg cell differentiation. While Aire+ TC I and III bore remarkable homology with Aire+ mTECs, including expression of tissue restricted self-antigens, TC IV lacked Aire expression and were enriched for molecules required for pTreg generation, including the TGF-β activating integrin αvβ8. Loss of either MHCII or Itgb8 expression by TCs led to a profound impairment in intestinal pTreg differentiation, with onset of intestinal inflammation. In contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical DCs was neither sufficient nor required for pTreg generation, further implicating TCs as the critical tolerogenic RORγt+ APC. Our studies reveal parallel pathways for establishment of tolerance to self and foreign antigen within the thymus and periphery, marked by involvement of shared cellular and transcriptional programs.
2022-09-06 | GSE174403 | GEO
Project description:Tolerance to self- or innocuous foreign antigens is vital for preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing AutoImmune Regulator, Aire, play a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development. A second wave of Treg cell differentiation occurs in the periphery, upon exposure to dietary and commensal microbiota derived antigens within the first few weeks of life, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells are not known. Here we identified a new lineage of tolerogenic RORγt+ antigen-presenting cells (APC) with a hybrid dendritic cell (DC)-mTEC phenotype, dubbed Thetis cells (TCs), comprising 4 major sub-groups (TC I-IV), We uncovered a developmental wave of TCs within intestinal lymph nodes during a critical early life window, coincident with the wave of pTreg cell differentiation. While Aire+ TC I and III bore remarkable homology with Aire+ mTECs, including expression of tissue restricted self-antigens, TC IV lacked Aire expression and were enriched for molecules required for pTreg generation, including the TGF-β activating integrin αvβ8. Loss of either MHCII or Itgb8 expression by TCs led to a profound impairment in intestinal pTreg differentiation, with onset of intestinal inflammation. In contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical DCs was neither sufficient nor required for pTreg generation, further implicating TCs as the critical tolerogenic RORγt+ APC. Our studies reveal parallel pathways for establishment of tolerance to self and foreign antigen within the thymus and periphery, marked by involvement of shared cellular and transcriptional programs.
2022-09-06 | GSE205066 | GEO
Project description:Tolerance to self- or innocuous foreign antigens is vital for preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing AutoImmune Regulator, Aire, play a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development. A second wave of Treg cell differentiation occurs in the periphery, upon exposure to dietary and commensal microbiota derived antigens within the first few weeks of life, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells are not known. Here we identified a new lineage of tolerogenic RORγt+ antigen-presenting cells (APC) with a hybrid dendritic cell (DC)-mTEC phenotype, dubbed Thetis cells (TCs), comprising 4 major sub-groups (TC I-IV), We uncovered a developmental wave of TCs within intestinal lymph nodes during a critical early life window, coincident with the wave of pTreg cell differentiation. While Aire+ TC I and III bore remarkable homology with Aire+ mTECs, including expression of tissue restricted self-antigens, TC IV lacked Aire expression and were enriched for molecules required for pTreg generation, including the TGF-β activating integrin αvβ8. Loss of either MHCII or Itgb8 expression by TCs led to a profound impairment in intestinal pTreg differentiation, with onset of intestinal inflammation. In contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical DCs was neither sufficient nor required for pTreg generation, further implicating TCs as the critical tolerogenic RORγt+ APC. Our studies reveal parallel pathways for establishment of tolerance to self and foreign antigen within the thymus and periphery, marked by involvement of shared cellular and transcriptional programs.
2022-09-06 | GSE205065 | GEO
Project description:Thetis cells (TCs), a recently identified family of RORgt+ antigen-presenting cells (APCs), comprise four subsets, including the TC IV subset that instructs tolerance to gut microbiota and food antigens. A developmental wave of TCs creates a window of opportunity for establishing intestinal tolerance during early life. However, the ontogeny of TCs and the cues that determine their abundance and heterogeneity are not known, limiting our ability to interrogate their functional roles and exploit their therapeutic potential. Here, we identify a RORgt+ TC and lymphoid tissue inducer (LTi) cell progenitor (TLP) that differentiates into the immediate RORgt+ TC progenitor (TCP) and the LTi progenitor (LTiP), with the transcription factor PU.1 determining TC fate. Despite their similarity to myeloid-derived classical dendritic cells (cDCs), we found that TCs were descended from the common lymphoid progenitor (CLP) with deletion of the plasmacytoid DC (pDC) lineage-determining transcription factor TCF4 leading to expansion of TLP and TCs, suggesting a shared developmental precursor with pDCs. TLP is enriched in mouse fetal liver, but in contrast to LTi cells, TCs emerge postnatally, pointing to a role for developmentally-timed environmental cues in promoting TCP differentiation. We identify one such cue–provision of RANKL by lymphoid tissue organizer cells–which was essential for TC I differentiation. Together, these findings identify the ontogeny of TCs and define the transcription factors that promote TC differentiation and heterogeneity. These insights will facilitate future investigations of these enigmatic cells, which have potential therapeutic applications in promoting tolerance.
2026-02-04 | GSE316304 | GEO
Project description:Thetis cells (TCs), a recently identified family of RORgt+ antigen-presenting cells (APCs), comprise four subsets, including the TC IV subset that instructs tolerance to gut microbiota and food antigens. A developmental wave of TCs creates a window of opportunity for establishing intestinal tolerance during early life. However, the ontogeny of TCs and the cues that determine their abundance and heterogeneity are not known, limiting our ability to interrogate their functional roles and exploit their therapeutic potential. Here, we identify a RORgt+ TC and lymphoid tissue inducer (LTi) cell progenitor (TLP) that differentiates into the immediate RORgt+ TC progenitor (TCP) and the LTi progenitor (LTiP), with the transcription factor PU.1 determining TC fate. Despite their similarity to myeloid-derived classical dendritic cells (cDCs), we found that TCs were descended from the common lymphoid progenitor (CLP) with deletion of the plasmacytoid DC (pDC) lineage-determining transcription factor TCF4 leading to expansion of TLP and TCs, suggesting a shared developmental precursor with pDCs. TLP is enriched in mouse fetal liver, but in contrast to LTi cells, TCs emerge postnatally, pointing to a role for developmentally-timed environmental cues in promoting TCP differentiation. We identify one such cue–provision of RANKL by lymphoid tissue organizer cells–which was essential for TC I differentiation. Together, these findings identify the ontogeny of TCs and define the transcription factors that promote TC differentiation and heterogeneity. These insights will facilitate future investigations of these enigmatic cells, which have potential therapeutic applications in promoting tolerance.
2026-02-04 | GSE316555 | GEO
Project description:Ontogeny and transcriptional regulation of Thetis cells
| PRJNA1403566 | ENA
Project description:Thetis cells (TCs), a recently identified family of RORgt+ antigen-presenting cells (APCs), comprise four subsets, including the TC IV subset that instructs tolerance to gut microbiota and food antigens1–6. A developmental wave of TCs creates a window of opportunity for establishing intestinal tolerance during early life1,5. However, the ontogeny of TCs and the cues that determine their abundance and heterogeneity are not known, limiting our ability to interrogate their functional roles and exploit their therapeutic potential. Here, we identify a RORgt+ TC and lymphoid tissue inducer (LTi) cell progenitor (TLP) that differentiates into the immediate RORgt+ TC progenitor (TCP) and the LTi progenitor (LTiP), with the transcription factor PU1 determining TC fate. Despite their similarity to myeloid-derived classical dendritic cells (cDCs), we found that TCs were descended from the common lymphoid progenitor (CLP) with deletion of the plasmacytoid DC (pDC) lineage-determining transcription factor TCF4 leading to expansion of TLP and TCs, suggesting a shared developmental precursor with pDCs. TLP is enriched in mouse fetal liver, but in contrast to LTi cells, TCs emerge postnatally, pointing to a role for developmentally-timed environmental cues in promoting TCP differentiation. We identify one such cue–provision of RANKL by lymphoid tissue organizer cells–which was essential for TC I differentiation. Together, these findings identify the ontogeny of TCs and define the transcription factors that promote TC differentiation and heterogeneity. These insights will facilitate future investigations of these enigmatic cells, which have potential therapeutic applications in promoting tolerance.
2026-02-04 | GSE316673 | GEO
Project description:Ontogeny and transcriptional regulation of Thetis cells [Flex]
| PRJNA1402262 | ENA