{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/127340"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/127340","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Identify the regulatory roles of intestinal secretory cell lineages during gut inflammation","abstract":"This thesis systematically investigates the roles of secretory intestinal epithelial cells, specifically tuft cells and enteroendocrine cells (EECs), in colonic inflammation, revealing novel cellular and molecular dynamics. The initial study utilized IEC-specific Hnrnp I knockout mice to demonstrate significant upregulation of pro-inflammatory cytokines such as Il1β, Cxcl1, and Ccl2. This animal model was thus validated in studying colitis progression and highlighted the potential of dietary interventions, such as the modified (MOD) diet, to alleviate inflammation. Subsequent research focused on tuft cells, revealing their role in mediating interactions between the intestinal epithelium and the immune system. This was characterized by L1CAM-mediated activation of type 2 innate lymphoid cells (ILC2s), which promoted secretion of Th2 cytokines IL4, IL6, and IL13, thus enhancing inflammatory responses. This pathway presents a potential target for therapeutic intervention, particularly in managing colon inflammation and cancer. The third study emphasized the regulatory role of EECs during colon inflammation, noting a significant increase in NR4A1 expression, which triggered immediate early genes (IEGs) activating the ATF4-ATF3 stress response pathway. Notably, changes in serotonin dynamics, including increased levels and serotonylation, were observed, suggesting that serotonylation may regulate cellular stress responses and contribute to cell proliferation during inflammatory conditions. Collectively, these findings illuminate the complex interplay of genetic, environmental, and dietary factors in modulating inflammatory responses in the colon, highlighting the significant roles of intestinal secretory cell lineages in orchestrating these responses through novel signaling pathways and interactions. The thesis shed light on potential therapeutic targets and suggests novel interventions, including the use of biologics and small molecule drugs, to modulate or ameliorate colon inflammation processes. Future research directions include pharmacological targeting of the L1CAM and NR4A nuclear receptor on certain epithelial cell types and exploring epigenetic regulation mechanisms such as serotonylation for therapeutic intervention treating either acute or chronic colitis.","abstract_html":"This thesis systematically investigates the roles of secretory intestinal epithelial cells, specifically tuft cells and enteroendocrine cells (EECs), in colonic inflammation, revealing novel cellular and molecular dynamics. The initial study utilized IEC-specific Hnrnp I knockout mice to demonstrate significant upregulation of pro-inflammatory cytokines such as Il1β, Cxcl1, and Ccl2. This animal model was thus validated in studying colitis progression and highlighted the potential of dietary interventions, such as the modified (MOD) diet, to alleviate inflammation. Subsequent research focused on tuft cells, revealing their role in mediating interactions between the intestinal epithelium and the immune system. This was characterized by L1CAM-mediated activation of type 2 innate lymphoid cells (ILC2s), which promoted secretion of Th2 cytokines IL4, IL6, and IL13, thus enhancing inflammatory responses. This pathway presents a potential target for therapeutic intervention, particularly in managing colon inflammation and cancer. The third study emphasized the regulatory role of EECs during colon inflammation, noting a significant increase in NR4A1 expression, which triggered immediate early genes (IEGs) activating the ATF4-ATF3 stress response pathway. Notably, changes in serotonin dynamics, including increased levels and serotonylation, were observed, suggesting that serotonylation may regulate cellular stress responses and contribute to cell proliferation during inflammatory conditions. Collectively, these findings illuminate the complex interplay of genetic, environmental, and dietary factors in modulating inflammatory responses in the colon, highlighting the significant roles of intestinal secretory cell lineages in orchestrating these responses through novel signaling pathways and interactions. The thesis shed light on potential therapeutic targets and suggests novel interventions, including the use of biologics and small molecule drugs, to modulate or ameliorate colon inflammation processes. Future research directions include pharmacological targeting of the L1CAM and NR4A nuclear receptor on certain epithelial cell types and exploring epigenetic regulation mechanisms such as serotonylation for therapeutic intervention treating either acute or chronic colitis.","abstract_has_math":false,"creators":["Xu, Guanying Bianca"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Food Science & Human Nutrition","degree_department":null,"school":null,"contributors":["Chen, Hong","Pan, Yuan-Xiang","Miller, Michael","Mei, Wenyan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-12","date_published":"2024-12","updated_at":"2026-07-22T22:25:03Z","subjects":["Intestinal Epithelial Cells","Colon Inflammation","Tuft Cells","Enteroendocrine Cells","Eecs","Serotonylation"],"languages":["eng","en"],"rights":["Copyright 2024 Guanying Xu"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/127340","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chen, Hong","Pan, Yuan-Xiang","Miller, Michael","Mei, Wenyan"]},{"key":"dc:creator","label":"Author","values":["Xu, Guanying Bianca"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-12","2024-11-12"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Food Science & Human Nutrition"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Intestinal Epithelial Cells","Colon Inflammation","Tuft Cells","Enteroendocrine Cells","Eecs","Serotonylation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng","en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2024 Guanying Xu"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/127340"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["This thesis systematically investigates the roles of secretory intestinal epithelial cells, specifically tuft cells and enteroendocrine cells (EECs), in colonic inflammation, revealing novel cellular and molecular dynamics. The initial study utilized IEC-specific Hnrnp I knockout mice to demonstrate significant upregulation of pro-inflammatory cytokines such as Il1β, Cxcl1, and Ccl2. This animal model was thus validated in studying colitis progression and highlighted the potential of dietary interventions, such as the modified (MOD) diet, to alleviate inflammation. Subsequent research focused on tuft cells, revealing their role in mediating interactions between the intestinal epithelium and the immune system. This was characterized by L1CAM-mediated activation of type 2 innate lymphoid cells (ILC2s), which promoted secretion of Th2 cytokines IL4, IL6, and IL13, thus enhancing inflammatory responses. This pathway presents a potential target for therapeutic intervention, particularly in managing colon inflammation and cancer. The third study emphasized the regulatory role of EECs during colon inflammation, noting a significant increase in NR4A1 expression, which triggered immediate early genes (IEGs) activating the ATF4-ATF3 stress response pathway. Notably, changes in serotonin dynamics, including increased levels and serotonylation, were observed, suggesting that serotonylation may regulate cellular stress responses and contribute to cell proliferation during inflammatory conditions. Collectively, these findings illuminate the complex interplay of genetic, environmental, and dietary factors in modulating inflammatory responses in the colon, highlighting the significant roles of intestinal secretory cell lineages in orchestrating these responses through novel signaling pathways and interactions. The thesis shed light on potential therapeutic targets and suggests novel interventions, including the use of biologics and small molecule drugs, to modulate or ameliorate colon inflammation processes. Future research directions include pharmacological targeting of the L1CAM and NR4A nuclear receptor on certain epithelial cell types and exploring epigenetic regulation mechanisms such as serotonylation for therapeutic intervention treating either acute or chronic colitis.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2026-12-01","The student, Guanying Xu, accepted the attached license on 2024-11-06 at 11:42.","The student, Guanying Xu, submitted this Dissertation for approval on 2024-11-06 at 11:55.","This Dissertation was approved for publication on 2024-11-12 at 13:06.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21298 on 2025-03-28 at 14:43:01"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Identify the regulatory roles of intestinal secretory cell lineages during gut inflammation"]}]}],"canonical_facts":{"dc:contributor":["Chen, Hong","Pan, Yuan-Xiang","Miller, Michael","Mei, Wenyan"],"dc:creator":["Xu, Guanying Bianca"],"dc:date":["2024-12","2024-11-12"],"dc:description":["This thesis systematically investigates the roles of secretory intestinal epithelial cells, specifically tuft cells and enteroendocrine cells (EECs), in colonic inflammation, revealing novel cellular and molecular dynamics. The initial study utilized IEC-specific Hnrnp I knockout mice to demonstrate significant upregulation of pro-inflammatory cytokines such as Il1β, Cxcl1, and Ccl2. This animal model was thus validated in studying colitis progression and highlighted the potential of dietary interventions, such as the modified (MOD) diet, to alleviate inflammation. Subsequent research focused on tuft cells, revealing their role in mediating interactions between the intestinal epithelium and the immune system. This was characterized by L1CAM-mediated activation of type 2 innate lymphoid cells (ILC2s), which promoted secretion of Th2 cytokines IL4, IL6, and IL13, thus enhancing inflammatory responses. This pathway presents a potential target for therapeutic intervention, particularly in managing colon inflammation and cancer. The third study emphasized the regulatory role of EECs during colon inflammation, noting a significant increase in NR4A1 expression, which triggered immediate early genes (IEGs) activating the ATF4-ATF3 stress response pathway. Notably, changes in serotonin dynamics, including increased levels and serotonylation, were observed, suggesting that serotonylation may regulate cellular stress responses and contribute to cell proliferation during inflammatory conditions. Collectively, these findings illuminate the complex interplay of genetic, environmental, and dietary factors in modulating inflammatory responses in the colon, highlighting the significant roles of intestinal secretory cell lineages in orchestrating these responses through novel signaling pathways and interactions. The thesis shed light on potential therapeutic targets and suggests novel interventions, including the use of biologics and small molecule drugs, to modulate or ameliorate colon inflammation processes. Future research directions include pharmacological targeting of the L1CAM and NR4A nuclear receptor on certain epithelial cell types and exploring epigenetic regulation mechanisms such as serotonylation for therapeutic intervention treating either acute or chronic colitis.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2026-12-01","The student, Guanying Xu, accepted the attached license on 2024-11-06 at 11:42.","The student, Guanying Xu, submitted this Dissertation for approval on 2024-11-06 at 11:55.","This Dissertation was approved for publication on 2024-11-12 at 13:06.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21298 on 2025-03-28 at 14:43:01"],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/127340"],"dc:language":["eng","en"],"dc:rights":["Copyright 2024 Guanying Xu"],"dc:subject":["Intestinal Epithelial Cells","Colon Inflammation","Tuft Cells","Enteroendocrine Cells","Eecs","Serotonylation"],"dc:title":["Identify the regulatory roles of intestinal secretory cell lineages during gut inflammation"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Food Science & Human Nutrition"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:03Z"}