Understanding T cell and gut interactions in early post-natal life
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Sharafianardakani, Zohreh
issued: 2025-10-31T07:00:00Z
issued: 2023
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Infants are susceptible to mucocutaneous candidiasis, which manifests via oral thrush and diaper rashes. Th17 cells are responsible for limiting mucosal invasion by commensal Candida spp. Dysregulated Th17 cells are also involved in necrotizing enterocolitis (NEC) pathogenesis, a surgical complication of the gut affecting about 5% of pre-term neonates. It was previously shown that neonatal peripheral blood naïve T cells produce low levels of IL-17, which might be protective against NEC while increasing susceptibility to mucocutaneous candidiasis. However, neonatal naïve CD4 T cells inherently produced high levels of IL-22 upon stimulation by Th17 cells. We sought the molecular mechanism underpinning the developmental lack of IL-17 responses in circulating blood T cells from neonates. A genome-wide transcriptome analysis comparing neonatal and adult naïve CD4 T cells revealed major developmental differences in the expression profile of genes associated with SMAD and STAT3 signaling. Functional assays confirmed that the requirement for TGF-β in human Th17 cell differentiation increased with age. Moreover, expression of STAT3 was relatively lower in neonatal naïve CD4 T cells; accordingly, overexpression of the STAT3 gene in naïve CD4 T cells restored IL-17 production in neonatal Th17 cells. Moreover, I generated infant (<6 months old)- and pediatric (6-14 years old)-derived enteroids and co-cultured them with recombinant human IL-22 and supernatant from Th17 cells, to investigate the effect of neonatal Th17 cells, a frequent type of T cell in the intestine, on the function of intestinal epithelial cells. I hypothesized that infants’ gut epithelium is developmentally different when compared to older children and that neonatal Th17 cell-produced IL-22 plays an important protective role in the gut. Indeed, I show that IL-22-treated enteroids upregulate antimicrobial genes such as Reg3𝛂⧸𝜸. Infant-derived enteroids also showed exaggerated proliferation and mucus production…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/84182
note: Understanding T cell and gut interactions in early post-natal life by Zohreh Sharafianardakani M.S., Simon Fraser University, 2015 M.S., Tarbiat Modarres University, 2012 B.Sc., Zanjan University, 2007 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2023 © Zohreh Sharafianardakani, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled Understanding T cell and gut interactions in early post-natal life submitted by Zohreh Sharafianardakani in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee Dr. Pascal Lavoie, Professor, Pediatrics, UBC Supervisor Dr. Bruce Vallance, Professor, Pediatrics, UBC Supervisory Committee Member Dr. Martin Hirst, Professor, Microbiology and Immunology, UBC Supervisory Committee Member Dr. Stefan Taubert, Associate Professor, Medical Genetics, UBC University Examiner Dr. Manon Ranger, Assistant Professor, Nursing, UBC University Examiner Additional Supervisory Committee Members: Dr. Gregor Reid, Associate Professor, Pediatrics, UBC Supervisory Committee Member iii Abstract Infants are susceptible to mucocutaneous candidiasis, which manifests via oral thrush and diaper rashes. Th17 cells are responsible for limiting mucosal invasion by commensal Candida spp. Dysregulated Th17 cells are also involved in necrotizing enterocolitis (NEC) pathogenesis, a surgical complication of the gut affecting about 5% of pre-term neonates. It was previously shown that neonatal peripheral blood naïve T cells produce low levels of IL-17, which might be protective against NEC while increasing susceptibility to mucocutaneous candidiasis. However, neonatal naïve CD4 T cells inherently produced high l…
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0430446
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Lavoie, Pascal M.
type: Text
identifier URI: http://hdl.handle.net/2429/84182