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Negative regulation of Type 2 immunity.

Chan, Pamela Yan-Ghi.

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Negative regulation of Type 2 immunity.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Negative regulation of Type 2 immunity./
Author:	Chan, Pamela Yan-Ghi.
Description:	152 p.
Notes:	Source: Dissertation Abstracts International, Volume: 76-11(E), Section: B.
Contained By:	Dissertation Abstracts International76-11B(E).
Subject:	Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3663474
ISBN:	9781321935851

Negative regulation of Type 2 immunity.
Chan, Pamela Yan-Ghi.

Negative regulation of Type 2 immunity. - 152 p.

Source: Dissertation Abstracts International, Volume: 76-11(E), Section: B.

Thesis (Ph.D.)--Yale University, 2015.

This item is not available from ProQuest Dissertations & Theses.

When the immune system is challenged, antigen-presenting cells (APC) initiate the innate immune response as the first line of defense followed by the instruction of T cell-mediated adaptive immunity. Even though APCs are fundamental for the orchestration of both the innate and adaptive arms, their activation must be tightly regulated otherwise immunopathology will result. Against helminth or allergen challenge, the immune system mounts a Type 2 immune response that is well characterized by the canonical cytokines IL-4, IL-5, IL-9 and IL-13, which result in eosinophilia, degranulation of mast cells and mucus production, which all serve to facilitate parasite or allergen expulsion but can instead result in immunopathology. Much remains unknown about how the Type 2 response is regulated. In this thesis, we show that genetic ablation of the TAM receptor tyrosine kinase Tyro3 leads to enhanced type 2 immune responses that result in increased protective immunity against helminths but enhanced susceptibility to allergic responses. Additionally, we have found that Protein S (PROS1), a key ligand for the TAM family of receptor tyrosine kinases expressed by APCs, is induced in T cells upon their activation. T cell-derived PROS 1 functions at the interface of innate and adaptive immunity to regulate the magnitude of the innate immune response by tempering APC activation. We have further discovered through analyses of in vitro-derived T subsets that Th2 cells are an abundant source of PROS 1. As in the absence of TYRO3, genetic ablation of the TAM ligand Pros] in T cells leads to enhanced type 2 immune responses. Additionally, PROS 1 is expressed in activated human T cells and its ability to regulate DC activation is conserved. Furthermore, meta-analysis of genome-wide association studies identifies TYRO3 as a new asthma susceptibility locus. Our results identify the TYRO3-PROS 1 axis as a key evolutionarily conserved anti-inflammatory mechanism that could be relevant to the regulation of Type 2 immune responses.

ISBN: 9781321935851Subjects--Topical Terms:

611031
Immunology.

Negative regulation of Type 2 immunity.
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245 1 0 $a Negative regulation of Type 2 immunity.
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500 $a Source: Dissertation Abstracts International, Volume: 76-11(E), Section: B.
500 $a Adviser: Carla V. Rothlin.
502 $a Thesis (Ph.D.)--Yale University, 2015.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a When the immune system is challenged, antigen-presenting cells (APC) initiate the innate immune response as the first line of defense followed by the instruction of T cell-mediated adaptive immunity. Even though APCs are fundamental for the orchestration of both the innate and adaptive arms, their activation must be tightly regulated otherwise immunopathology will result. Against helminth or allergen challenge, the immune system mounts a Type 2 immune response that is well characterized by the canonical cytokines IL-4, IL-5, IL-9 and IL-13, which result in eosinophilia, degranulation of mast cells and mucus production, which all serve to facilitate parasite or allergen expulsion but can instead result in immunopathology. Much remains unknown about how the Type 2 response is regulated. In this thesis, we show that genetic ablation of the TAM receptor tyrosine kinase Tyro3 leads to enhanced type 2 immune responses that result in increased protective immunity against helminths but enhanced susceptibility to allergic responses. Additionally, we have found that Protein S (PROS1), a key ligand for the TAM family of receptor tyrosine kinases expressed by APCs, is induced in T cells upon their activation. T cell-derived PROS 1 functions at the interface of innate and adaptive immunity to regulate the magnitude of the innate immune response by tempering APC activation. We have further discovered through analyses of in vitro-derived T subsets that Th2 cells are an abundant source of PROS 1. As in the absence of TYRO3, genetic ablation of the TAM ligand Pros] in T cells leads to enhanced type 2 immune responses. Additionally, PROS 1 is expressed in activated human T cells and its ability to regulate DC activation is conserved. Furthermore, meta-analysis of genome-wide association studies identifies TYRO3 as a new asthma susceptibility locus. Our results identify the TYRO3-PROS 1 axis as a key evolutionarily conserved anti-inflammatory mechanism that could be relevant to the regulation of Type 2 immune responses.
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