{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1949"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1949","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Regulation of Murine Mast Cell Homeostasis by TGF-β1 and CD4+CD25+C Regulatory T Cells","abstract":"Understanding mast cell development is central to allergic disease pathophysiology. Our laboratory has previously shown that cytokines such as IL-4 and IL-10 inhibit mast cell development from bone marrow progenitors. These studies encouraged our interest in other regulatory cytokines, including transforming growth factor β1 (TGF- β1). TGF- β1 has many cellular sources, one of which is CD4+CD25 regulatory T cells (Tregs). We wanted to determine the effects of Transforming Growth Factor (TGF) βl on mast cell development. We find that TGFβl decreased FcεRI, c-Kit, T1/ST2 and FcεR expression, and inhibited granule formation in developing mast cells. Accessory cells were not required for this inhibition. Smad3-deficiency did not alter the response of bone marrow cells to TGFβ1. TGFβl inhibited expression of the FcεRI a subunit protein, without decreasing β or γ proteins. Mast cells derived in the presence of TGFβl were functionally impaired, as IgE-mediated cytokine secretion was greatly reduced. The changes in granule formation and surface antigen expression were long-standing, as they were not reversed by transfer to W/WV mice. The TGF-β1 dependent transcriptional regulation of bone marrow cells from which mast cells develop was examined through DNA microarray analysis. Wild type (WT) bone marrow cells were stimulated with IL-3+SCF+vehicle or IL-3+SCF+TGF-βI for 10 days and their transcriptomes* analyzed. The results identified which components of transcriptional regulation were regulated by TGF- β1. Of particular interest was the upregulation of the β subunit of the FcεRI, inspite of no receptor surface expression and the differential regulation of various mast cell proteases (MCPs). This initial survey provides a potential starting point for further analysis of the role of TGF-β1 -dependent signaling in developing mast cells. Because they produce TGF-β1 and/or IL-10, regulatory T cell-dependent murine mast cell inhibition was examined. Co-culture of mast cells with regulatory T cells for 6 days downregulated mast cell number, high affinity IgE receptor and c-Kit surface expression. This led to a decrease in TNFa release making mast cells functionally impaired. By using Tregs from IL-10 KO mice, this effect was proven to be IL-10 dependent. Mast cells are mediators of inflammatory disease. TGFβl and IL-10 may contribute to mast cell homeostasis by inhibiting maturation from bone marrow precursors. The effects of TGFβ1 and regulatory T cell derived IL-10 result in greatly diminished expression of cell surface markers, reduced granulation, and lack of responsiveness to IgE-mediated activation. Thus TGFβl and/or CD+CD25+ T cells can serve as potent and multifunctional regulators of mast cell maturation and/or function.* A set of genes that are expressed in a cell at any given time.","abstract_html":"Understanding mast cell development is central to allergic disease pathophysiology. Our laboratory has previously shown that cytokines such as IL-4 and IL-10 inhibit mast cell development from bone marrow progenitors. These studies encouraged our interest in other regulatory cytokines, including transforming growth factor β1 (TGF- β1). TGF- β1 has many cellular sources, one of which is CD4+CD25 regulatory T cells (Tregs). We wanted to determine the effects of Transforming Growth Factor (TGF) βl on mast cell development. We find that TGFβl decreased FcεRI, c-Kit, T1/ST2 and FcεR expression, and inhibited granule formation in developing mast cells. Accessory cells were not required for this inhibition. Smad3-deficiency did not alter the response of bone marrow cells to TGFβ1. TGFβl inhibited expression of the FcεRI a subunit protein, without decreasing β or γ proteins. Mast cells derived in the presence of TGFβl were functionally impaired, as IgE-mediated cytokine secretion was greatly reduced. The changes in granule formation and surface antigen expression were long-standing, as they were not reversed by transfer to W/WV mice. The TGF-β1 dependent transcriptional regulation of bone marrow cells from which mast cells develop was examined through DNA microarray analysis. Wild type (WT) bone marrow cells were stimulated with IL-3+SCF+vehicle or IL-3+SCF+TGF-βI for 10 days and their transcriptomes* analyzed. The results identified which components of transcriptional regulation were regulated by TGF- β1. Of particular interest was the upregulation of the β subunit of the FcεRI, inspite of no receptor surface expression and the differential regulation of various mast cell proteases (MCPs). This initial survey provides a potential starting point for further analysis of the role of TGF-β1 -dependent signaling in developing mast cells. Because they produce TGF-β1 and/or IL-10, regulatory T cell-dependent murine mast cell inhibition was examined. Co-culture of mast cells with regulatory T cells for 6 days downregulated mast cell number, high affinity IgE receptor and c-Kit surface expression. This led to a decrease in TNFa release making mast cells functionally impaired. By using Tregs from IL-10 KO mice, this effect was proven to be IL-10 dependent. Mast cells are mediators of inflammatory disease. TGFβl and IL-10 may contribute to mast cell homeostasis by inhibiting maturation from bone marrow precursors. The effects of TGFβ1 and regulatory T cell derived IL-10 result in greatly diminished expression of cell surface markers, reduced granulation, and lack of responsiveness to IgE-mediated activation. Thus TGFβl and/or CD+CD25+ T cells can serve as potent and multifunctional regulators of mast cell maturation and/or function.* A set of genes that are expressed in a cell at any given time.","abstract_has_math":false,"creators":["Kashyap, Mohit"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Microbiology & Immunology","degree_department":null,"school":null,"contributors":["Dr. John J. Ryan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T05:54:40Z","subjects":["cellular signal","immune suppression","bone marrow","Medicine and Health Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/950"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/950","href":"https://scholarscompass.vcu.edu/etd/950","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/8AET-Y905","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. John J. 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Our laboratory has previously shown that cytokines such as IL-4 and IL-10 inhibit mast cell development from bone marrow progenitors. These studies encouraged our interest in other regulatory cytokines, including transforming growth factor β1 (TGF- β1). TGF- β1 has many cellular sources, one of which is CD4+CD25 regulatory T cells (Tregs). We wanted to determine the effects of Transforming Growth Factor (TGF) βl on mast cell development. We find that TGFβl decreased FcεRI, c-Kit, T1/ST2 and FcεR expression, and inhibited granule formation in developing mast cells. Accessory cells were not required for this inhibition. Smad3-deficiency did not alter the response of bone marrow cells to TGFβ1. TGFβl inhibited expression of the FcεRI a subunit protein, without decreasing β or γ proteins. Mast cells derived in the presence of TGFβl were functionally impaired, as IgE-mediated cytokine secretion was greatly reduced. The changes in granule formation and surface antigen expression were long-standing, as they were not reversed by transfer to W/WV mice. The TGF-β1 dependent transcriptional regulation of bone marrow cells from which mast cells develop was examined through DNA microarray analysis. Wild type (WT) bone marrow cells were stimulated with IL-3+SCF+vehicle or IL-3+SCF+TGF-βI for 10 days and their transcriptomes* analyzed. The results identified which components of transcriptional regulation were regulated by TGF- β1. Of particular interest was the upregulation of the β subunit of the FcεRI, inspite of no receptor surface expression and the differential regulation of various mast cell proteases (MCPs). This initial survey provides a potential starting point for further analysis of the role of TGF-β1 -dependent signaling in developing mast cells. Because they produce TGF-β1 and/or IL-10, regulatory T cell-dependent murine mast cell inhibition was examined. Co-culture of mast cells with regulatory T cells for 6 days downregulated mast cell number, high affinity IgE receptor and c-Kit surface expression. This led to a decrease in TNFa release making mast cells functionally impaired. By using Tregs from IL-10 KO mice, this effect was proven to be IL-10 dependent. Mast cells are mediators of inflammatory disease. TGFβl and IL-10 may contribute to mast cell homeostasis by inhibiting maturation from bone marrow precursors. The effects of TGFβ1 and regulatory T cell derived IL-10 result in greatly diminished expression of cell surface markers, reduced granulation, and lack of responsiveness to IgE-mediated activation. Thus TGFβl and/or CD+CD25+ T cells can serve as potent and multifunctional regulators of mast cell maturation and/or function.* A set of genes that are expressed in a cell at any given time."]},{"key":"dc:title","label":"Title","values":["Regulation of Murine Mast Cell Homeostasis by TGF-β1 and CD4+CD25+C Regulatory T Cells"]}]}],"canonical_facts":{"dc:contributor":["Dr. John J. Ryan"],"dc:creator":["Kashyap, Mohit"],"dc:date.available":["2014-07-09T07:00:00Z"],"dc:description.abstract":["Understanding mast cell development is central to allergic disease pathophysiology. Our laboratory has previously shown that cytokines such as IL-4 and IL-10 inhibit mast cell development from bone marrow progenitors. These studies encouraged our interest in other regulatory cytokines, including transforming growth factor β1 (TGF- β1). TGF- β1 has many cellular sources, one of which is CD4+CD25 regulatory T cells (Tregs). We wanted to determine the effects of Transforming Growth Factor (TGF) βl on mast cell development. We find that TGFβl decreased FcεRI, c-Kit, T1/ST2 and FcεR expression, and inhibited granule formation in developing mast cells. Accessory cells were not required for this inhibition. Smad3-deficiency did not alter the response of bone marrow cells to TGFβ1. TGFβl inhibited expression of the FcεRI a subunit protein, without decreasing β or γ proteins. Mast cells derived in the presence of TGFβl were functionally impaired, as IgE-mediated cytokine secretion was greatly reduced. The changes in granule formation and surface antigen expression were long-standing, as they were not reversed by transfer to W/WV mice. The TGF-β1 dependent transcriptional regulation of bone marrow cells from which mast cells develop was examined through DNA microarray analysis. Wild type (WT) bone marrow cells were stimulated with IL-3+SCF+vehicle or IL-3+SCF+TGF-βI for 10 days and their transcriptomes* analyzed. The results identified which components of transcriptional regulation were regulated by TGF- β1. Of particular interest was the upregulation of the β subunit of the FcεRI, inspite of no receptor surface expression and the differential regulation of various mast cell proteases (MCPs). This initial survey provides a potential starting point for further analysis of the role of TGF-β1 -dependent signaling in developing mast cells. Because they produce TGF-β1 and/or IL-10, regulatory T cell-dependent murine mast cell inhibition was examined. Co-culture of mast cells with regulatory T cells for 6 days downregulated mast cell number, high affinity IgE receptor and c-Kit surface expression. This led to a decrease in TNFa release making mast cells functionally impaired. By using Tregs from IL-10 KO mice, this effect was proven to be IL-10 dependent. Mast cells are mediators of inflammatory disease. TGFβl and IL-10 may contribute to mast cell homeostasis by inhibiting maturation from bone marrow precursors. The effects of TGFβ1 and regulatory T cell derived IL-10 result in greatly diminished expression of cell surface markers, reduced granulation, and lack of responsiveness to IgE-mediated activation. Thus TGFβl and/or CD+CD25+ T cells can serve as potent and multifunctional regulators of mast cell maturation and/or function.* A set of genes that are expressed in a cell at any given time."],"dc:identifier":["https://doi.org/10.25772/8AET-Y905","https://scholarscompass.vcu.edu/etd/950"],"dc:rights":["© The Author"],"dc:subject":["cellular signal","immune suppression","bone marrow","Medicine and Health Sciences"],"dc:title":["Regulation of Murine Mast Cell Homeostasis by TGF-β1 and CD4+CD25+C Regulatory T Cells"],"thesis:degree_discipline":["Microbiology & Immunology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:54:40Z"}