Development and heterogeneity of type 2 innate lymphoid cells in mouse lungs
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Ghaedi, Maryam
issued: 2020-07-31T07:00:00Z
issued: 2019
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. To investigate the early developmental pathways that leads to the generation of lung ILC2, I divided adult bone marrow lymphoid primed multipotent progenitor (LMPPs) into CD127⁻ (LMPP-s) and CD127⁺ (LMPP+s) subsets and compared them with Ly6D⁻ and Ly6D⁺ common lymphoid progenitors (CLPs). Although, all lymphocytes are thought to develop from CLPs, LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. These results suggested that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways. To investigate whether distinct ILC2 subsets mediate the distinct ILC2 functions and elucidate their developmental relationship, we generated RORα lineage tracer mice and analyzed them by single cell RNA sequencing, flow cytometry and functional assays. Adult lung ILC2s were divided into IL-18Rα⁺ST2⁻ and IL-18Rα⁻ST2⁺ subsets. The former had an immature ILC phenotype, produced little cytokines and contained ILC progenitor like cells expressing Tcf7, whereas the latter was conventional ILC2s. Neonatal lung conventional ILC2s (IL-18Rα⁻ST2⁺) were divided into two distinct effector subsets and an IL-18Rα⁺ST2⁻Tcf7⁺ progenitor-like subset. The two effector subsets were defined by the expression of ICOS and KLRG1, and they differentially produced the growth-factor amphiregulin and type 2 cytokines. Therefore, effector ILC2s diverge into tissue-repairing and pro-inflammatory subsets, which differ in transcriptional and phenotypic properties. The IL-18Rα⁺ST2⁻Tcf7⁺ cells are likely IL-18 responsive lung ILC progenitors, which may contribute to ILC-poiesis in neonatal and inflamed lungs.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/70968
note: DEVELOPMENT AND HETEROGENEITY OF TYPE 2 INNATE LYMPHOID CELLS IN MOUSE LUNGS by Maryam Ghaedi M.S., The University of British Columbia, 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pathology and Laboratory Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2019 © Maryam Ghaedi, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Development and heterogeneity of type 2 innate lymphoid cells in mouse lungs submitted by Maryam Ghaedi in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pathology and Laboratory Medicine Examining Committee: Dr. Fumio Takei Supervisor Dr. Ninan Abraham Supervisory Committee Member Dr. Pauline Johnson Supervisory Committee Member Dr. Megan Levings University Examiner Dr. Andrew Weng University Examiner Additional Supervisory Committee Members: Dr. Gerry Krystal Supervisory Committee Member Dr. William Lockwood Supervisory Committee Member iii Abstract Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. To investigate the early developmental pathways that leads to the generation of lung ILC2, I divided adult bone marrow lymphoid primed multipotent progenitor (LMPPs) into CD127− (LMPP-s) and CD127+ (LMPP+s) subsets and compared them with Ly6D− and Ly6D+ common lymphoid progenitors (CLPs). Although, all lymphocytes are thought to develop from CLPs, LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. These results suggested that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways. To investigate whether distinct ILC2 subsets mediate the distinct ILC2 functions and elucidate their developmental relationship, we generated RORα lineage …
has type: Thesis/Dissertation
date issued: 2019-09
is shown at: 10.14288/1.0379816
language: eng
degree discipline: Pathology and Laboratory 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
type: Text
identifier URI: http://hdl.handle.net/2429/70968