Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic acid (poly I:C)-induced cDC1 maturation in a STAT3-dependent manner. Transcriptome analyses further revealed that although poly I:C induces numerous inflammatory pathways in cDC1s, interferon (IFN) signaling was selectively inhibited by IL-10 and STAT3. Furthermore, assessment of the relative contribution of each IFN type indicated that type I IFN is the primary target of STAT3-mediated inhibition. To determine the impact of these signaling events on cDC1 induction of T cell-mediated immunity, we utilized a cell-based cDC1 anti-tumor vaccine strategy. STAT3 and IL-10 were found to impede the ability of cDC1 vaccination to restrain tumor growth. In addition, both CD8+ T cell and CD4+ T helper cell responses induced by cDC1 vaccination were inhibited by STAT3. Taken together, we conclude that STAT3 inhibits cDC1-induced anti-tumor immunity and cDC1 type I IFN signaling. As cDC1s are essential for the induction of T cell-mediated immunity, these findings could provide rationale for development of novel immunotherapies for cancer and other immune diseases.
","abstract_html":"<p>Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic acid (poly I:C)-induced cDC1 maturation in a STAT3-dependent manner. Transcriptome analyses further revealed that although poly I:C induces numerous inflammatory pathways in cDC1s, interferon (IFN) signaling was selectively inhibited by IL-10 and STAT3. Furthermore, assessment of the relative contribution of each IFN type indicated that type I IFN is the primary target of STAT3-mediated inhibition. To determine the impact of these signaling events on cDC1 induction of T cell-mediated immunity, we utilized a cell-based cDC1 anti-tumor vaccine strategy. STAT3 and IL-10 were found to impede the ability of cDC1 vaccination to restrain tumor growth. In addition, both CD8<sup>+</sup> T cell and CD4<sup>+</sup> T helper cell responses induced by cDC1 vaccination were inhibited by STAT3. Taken together, we conclude that STAT3 inhibits cDC1-induced anti-tumor immunity and cDC1 type I IFN signaling. As cDC1s are essential for the induction of T cell-mediated immunity, these findings could provide rationale for development of novel immunotherapies for cancer and other immune diseases.</p>","abstract_has_math":false,"creators":["Chrisikos, Taylor","0000-0001-8966-4046
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Stephanie S. Watowich","Shao-Cong Sun","James Allison"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-12-01T08:00:00Z","date_published":"2021-12-01T08:00:00Z","updated_at":"2026-07-24T05:48:47Z","subjects":["Dendritic cells","cDC1s","IFNs","tumor microenvironment","tumor immunology","dendritic cell vaccine","immunosuppression","Cancer Biology","Immunity","Immunotherapy"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1144","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Stephanie S. Watowich","Shao-Cong Sun","James Allison"]},{"key":"dc:creator","label":"Author","values":["Chrisikos, Taylor","0000-0001-8966-4046
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"]},{"key":"dc:title","label":"Title","values":["Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells"]}]}],"canonical_facts":{"dc:contributor":["Stephanie S. Watowich","Shao-Cong Sun","James Allison"],"dc:creator":["Chrisikos, Taylor","0000-0001-8966-4046
"],"dc:date.available":["2022-09-29T07:00:00Z"],"dc:description.abstract":["Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic acid (poly I:C)-induced cDC1 maturation in a STAT3-dependent manner. Transcriptome analyses further revealed that although poly I:C induces numerous inflammatory pathways in cDC1s, interferon (IFN) signaling was selectively inhibited by IL-10 and STAT3. Furthermore, assessment of the relative contribution of each IFN type indicated that type I IFN is the primary target of STAT3-mediated inhibition. To determine the impact of these signaling events on cDC1 induction of T cell-mediated immunity, we utilized a cell-based cDC1 anti-tumor vaccine strategy. STAT3 and IL-10 were found to impede the ability of cDC1 vaccination to restrain tumor growth. In addition, both CD8+ T cell and CD4+ T helper cell responses induced by cDC1 vaccination were inhibited by STAT3. Taken together, we conclude that STAT3 inhibits cDC1-induced anti-tumor immunity and cDC1 type I IFN signaling. As cDC1s are essential for the induction of T cell-mediated immunity, these findings could provide rationale for development of novel immunotherapies for cancer and other immune diseases.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1144"],"dc:subject":["Dendritic cells","cDC1s","IFNs","tumor microenvironment","tumor immunology","dendritic cell vaccine","immunosuppression","Cancer Biology","Immunity","Immunotherapy"],"dc:title":["Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:48:47Z"}