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The Role of Type 2 Cytokines in Tissue Homeostasis and Regeneration.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of Type 2 Cytokines in Tissue Homeostasis and Regeneration./
Author:	Chen, Francis M.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2022,
Description:	175 p.
Notes:	Source: Dissertations Abstracts International, Volume: 84-01, Section: B.
Contained By:	Dissertations Abstracts International84-01B.
Subject:	Histology. -
ISBN:	9798802756430

The Role of Type 2 Cytokines in Tissue Homeostasis and Regeneration.
Chen, Francis M.

The Role of Type 2 Cytokines in Tissue Homeostasis and Regeneration. - Ann Arbor : ProQuest Dissertations & Theses, 2022 - 175 p.

Source: Dissertations Abstracts International, Volume: 84-01, Section: B.

Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2022.

Innate immune signaling molecules have been observed to have pleiotropic effects regulating a wide range of cell types and tissues. Signaling molecules such as the type-2 associated cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13), classically defined by their anti-inflammatory effects during inflammation, have been found to modify various cell populations in the tissue niche such as regulating tissue metabolism and expanding stem cell populations after injury. However, the processes by which these type 2 cytokines shape the niche to sustain homeostasis is not entirely clear. This dissertation aims to address the extent and mechanism by which IL-4 and IL13 regulate niche cellular composition and internal cellular processes to maintain homeostasis. Here I utilized two distinct models of dysregulated homeostasis in different tissue types at both the tissue and cellular level to determine the processes regulated by IL-4 and IL-13 to drive the system to an equilibrium conducive for the well-being of an organism. Specifically, I examined how the distinct neonatal immune system, preferring a TH2 response driven by IL-4 and IL-13, would respond after ischemic injury. I observed that the IL-4/IL-13 driven basal neonatal immune system, different from immune profile of an adult, actively promotes an anti-inflammatory phenotype across various immune cell types in the neonatal cardiac niche after ischemic injury induced by the ligation of the left anterior descending coronary artery. Loss of IL-4 and IL-13, modelled using a IL-4/IL-13 knockout mouse, exhibited functional defects after injury using echocardiography while flow cytometric analysis further indicated a pro-inflammatory response by immune cells, ii antithetical to cardiac repair. These results confirmed the positive role of IL-4 and IL-13 on cardiac regeneration in the neonate at a tissue level by regulating niche immune cellular composition to an anti-inflammatory state. Concurrently, I examined the effects of type 2 signals on a cellular level. Using an in vitro cell model of neurodegeneration, I observed that a proliferation defect in neural progenitor cells derived from a Spinocerebellar Ataxia 3 (SCA3) patient was restored after treatment with IL-4. Specifically, IL-4 upregulated autophagic programs while downregulating apoptosis. These results further expand on the role type 2 immune signals in regulating cellular homeostasis. In summary, the findings from my thesis work denote the indispensability and broad range effects of type 2 cytokines outside the classical anti-inflammatory immune regulatory response by modulating tissue and cellular components to perpetuate homeostasis.

ISBN: 9798802756430Subjects--Topical Terms:

641250
Histology.
Subjects--Index Terms:

Cytokines

The Role of Type 2 Cytokines in Tissue Homeostasis and Regeneration.
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245 1 4 $a The Role of Type 2 Cytokines in Tissue Homeostasis and Regeneration.
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520 $a Innate immune signaling molecules have been observed to have pleiotropic effects regulating a wide range of cell types and tissues. Signaling molecules such as the type-2 associated cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13), classically defined by their anti-inflammatory effects during inflammation, have been found to modify various cell populations in the tissue niche such as regulating tissue metabolism and expanding stem cell populations after injury. However, the processes by which these type 2 cytokines shape the niche to sustain homeostasis is not entirely clear. This dissertation aims to address the extent and mechanism by which IL-4 and IL13 regulate niche cellular composition and internal cellular processes to maintain homeostasis. Here I utilized two distinct models of dysregulated homeostasis in different tissue types at both the tissue and cellular level to determine the processes regulated by IL-4 and IL-13 to drive the system to an equilibrium conducive for the well-being of an organism. Specifically, I examined how the distinct neonatal immune system, preferring a TH2 response driven by IL-4 and IL-13, would respond after ischemic injury. I observed that the IL-4/IL-13 driven basal neonatal immune system, different from immune profile of an adult, actively promotes an anti-inflammatory phenotype across various immune cell types in the neonatal cardiac niche after ischemic injury induced by the ligation of the left anterior descending coronary artery. Loss of IL-4 and IL-13, modelled using a IL-4/IL-13 knockout mouse, exhibited functional defects after injury using echocardiography while flow cytometric analysis further indicated a pro-inflammatory response by immune cells, ii antithetical to cardiac repair. These results confirmed the positive role of IL-4 and IL-13 on cardiac regeneration in the neonate at a tissue level by regulating niche immune cellular composition to an anti-inflammatory state. Concurrently, I examined the effects of type 2 signals on a cellular level. Using an in vitro cell model of neurodegeneration, I observed that a proliferation defect in neural progenitor cells derived from a Spinocerebellar Ataxia 3 (SCA3) patient was restored after treatment with IL-4. Specifically, IL-4 upregulated autophagic programs while downregulating apoptosis. These results further expand on the role type 2 immune signals in regulating cellular homeostasis. In summary, the findings from my thesis work denote the indispensability and broad range effects of type 2 cytokines outside the classical anti-inflammatory immune regulatory response by modulating tissue and cellular components to perpetuate homeostasis.
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