Characterization of lamprey IL-17 family members and their receptors Público

Abstract

Interleukin-17 is an ancient cytokine implicated in a variety of immune defense mechanisms. We have indentified five members of the sea lamprey IL-17 family (IL-17-1 to IL-17-5) and six IL-17 receptor genes (IL-17R1 to IL-17R6), determined their relationship with mammalian orthologues, and examined their expression patterns and potential interactions in order to explore their potential roles in innate and adaptive immunity. The most highly expressed IL-17 family member is IL-17-4 (mammalian IL-17D like), which was found to be preferentially expressed by epithelial cells of skin, intestine and gills and by the two types of lamprey T-like cells. IL-17-4 binds to recombinant IL-17R1 and to the surface of IL-17R1-expressing B-like cells and monocytes. Treatment of lamprey blood cells with recombinant IL-17-4 protein enhanced the transcription of genes expressed by B-like cells. These findings suggest an IL-17 mediated mechanism for coordinating the interaction of T-like cells with cells of the adaptive and innate immune systems in jawless vertebrates.

Table of Contents

Chapter 1: General Introduction 1

1.1 IL-17s and their receptors in mammals 2

1.2 IL-17s and their receptors in invertebrates and fish 19

1.3 Lamprey VLR immune system 22

1.4 Summary of aims of the study 29

Chapter 2: Characterization of lamprey IL-17 family members 37

2.1 Abstract 38

2.2 Introduction 38

2.3 Materials and Methods 41

2.4 Results 48

2.5 Discussion 52

Chapter 3: Characterization of lamprey IL-17 receptor family members 75

3.1 Abstract 76

3.2 Introduction 76

3.3 Materials and Methods 78

3.4 Results 83

3.5 Discussion 88

Chapter 4: Conclusions and Future directions 113

4.1 Summary and conclusions 114

4.2 Remaining questions and future directions 116

References 124

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Genetics and Molecular Biology
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Biology, Molecular
Palabra Clave	interleukin-17 interleukin-17 receptor lamprey
Committee Chair / Thesis Advisor	Cooper, Max Dale, Emory University
Committee Members	Boss, Jeremy, Emory University Zhou, Wei, Emory University Neish, Andrew S, Emory University Amara, Rama Rao, Emory University

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