Regulation of inflammatory signaling in health and disease

253 Pages·2017·4.651 MB·English

by  Xu, Dakang

Advances in Experimental Medicine and Biology 1024
Dakang Xu Editor
Regulation of
Inflammatory
Signaling in
Health and
Disease
Advances in Experimental Medicine
and Biology
Volume 1024
Editorial Board
IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research,
Orangeburg, NY, USA
JOHN D. LAMBRIS, University of Pennsylvania,
Philadelphia, PA, USA
RODOLFO PAOLETTI, University of Milan, Milan, Italy
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Dakang Xu
Editor
Regulation of Inflammatory
Signaling in Health and
Disease
Editor
Dakang Xu
Faculty of Medical Laboratory Science, Ruijin Hospital
Shanghai Jiao Tong University School of Medicine
Shanghai, China
ISSN 0065-2598 ISSN 2214-8019 (electronic)
Advances in Experimental Medicine and Biology
ISBN 978-981-10-5986-5 ISBN 978-981-10-5987-2 (eBook)
DOI 10.1007/978-981-10-5987-2
Library of Congress Control Number: 2017952362
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Preface
The innate immune system provides immediate defense against invading microbial
pathogens and is found in all classes of living organisms, whereas the adaptive
immune system is found only in vertebrates. This book covers recent research in
innate immunity that has revealed a large number of receptors that sense the pres-
ence of microorganisms or cellular damage in tissues. In complex tissues, many of
these sensing events occur simultaneously. Thus, downstream signaling pathways
need to be integrated so that an appropriate inflammatory response can be
initiated.
Current key concepts in innate immunity are discussed, including the formation
of signalosomes, inflammasome formation and pyroptosis, methods of extrinsic cell
communication, and examples of receptor cooperation. There is an overview of
posttranslational modifications in different inflammatory signaling pathways and
their essential roles in the regulation of inflammation. Emerging evidence suggests
that epigenetic mechanisms play an important role in fine tuning the innate immune
response. An understanding of epigenetic regulation of innate immune cell identity
and function will enable elucidation of the relationship between gene-specific host
defense and inflammatory diseases, as well as innate immune memory in health and
disease. Inflammasomes determine the molecular and cellular processes of inflam-
mation in response to microbial infection. Current data suggest that inflammasomes
also have antimicrobial functions. Microbial factors are involved in regulating host
inflammatory signaling pathways, the composition and load of the gut microbiota,
the co-metabolism of the host and the microbiota, and the host immune system and
physiology.
Novel aspects of functional genomics, epigenomics, transcriptomics, posttrans-
lational modifications, the microbiome, and immunometabolism are reviewed in
relation to inflammatory signaling and responses. Study of the inflammation that
occurs in response to host-pathogen interactions is essential for the development of
new therapies to improve human health. Here we review recent findings on the
mechanisms underlying the regulation of inflammatory responses to pathogens,
dysregulation of these responses in inflammatory disease, and the use of such mech-
anisms to boost or subdue the inflammatory response. Such as TLR agonists as
v
vi Preface
adjuvants for cancer vaccines, small-molecule HDAC inhibitors and other epigen-
etic regulators as drug targets in inflammatory diseases, and the potential role of
miR-155 as a diagnostic, prognostic, and therapeutic target in the treatment of mul-
tiple sclerosis.
The cGAS–STING pathway detects the presence of cytosolic DNA and triggers
the expression of inflammatory genes in response to DNA damage. It is also linked
to the tumor microenvironment, where it is paramount to immune clearance of
tumors. To date, little attention has been paid to the aging-associated alteration in
intercellular communication known as “inflammaging,” a proinflammatory pheno-
type in organs that occurs with aging, suggesting an alternative senescence-
associated secretory phenotype. Telomere attrition induces not only epithelial stem
cell senescence, but also low-grade inflammation in lungs.
We also review crosstalk between the innate and adaptive immune systems, in
particular in relation to the newly emerged innate lymphoid cells (ILCs). Innate
lymphoid cells are involved in both innate and adaptive immunity, and contribute to
tissue homeostasis, as well as defense against pathogens and inflammatory
disorders.
Finally, I thank all the authors for their valuable contributions. It is my hope that
this book will stimulate scientists and clinicians to continue to explore this fascinat-
ing field. Bridging the gaps in understanding between the fields of human and
mouse immunology will provide new insights into inflammatory-mediated disease
and immune defense. These innovative perspectives in basic and clinical research
will aid in the translation of knowledge to the clinic.
Shanghai, China Dakang Xu
Contents
1 Activation of the Innate Immune Receptors: Guardians
of the Micro Galaxy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Dominic De Nardo
2 Posttranslational Modification Control
of Inflammatory Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Yibo Si, Yunlu Zhang, Zijuan Chen, Ruixue Zhou,
Yihua Zhang, Doudou Hao, and Dapeng Yan
3 Emerging Roles for Epigenetic Programming in the Control
of Inflammatory Signaling Integration in Heath and Disease . . . . . . 63
Yiqun Hu, Feng Yan, Le Ying, and Dakang Xu
4 Roles of HDACs in the Responses of Innate Immune Cells
and as Targets in Inflammatory Diseases . . . . . . . . . . . . . . . . . . . . . . . 91
Yiqun Hu and Bandar Ali Suliman
5 miR-155 Dysregulation and Therapeutic Intervention
in Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Claire E. McCoy
6 Inflammasomes in the Gut Mucosal Homeostasis . . . . . . . . . . . . . . . . 133
Xiaomin Yao and Guangxun Meng
7 Microbial Factors in Inflammatory Diseases and Cancers . . . . . . . . . 153
Hong Sheng Ong and Howard Chi Ho Yim
8 cGAS-STING Activation in the Tumor Microenvironment
and Its Role in Cancer Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Geneviève Pépin and Michael P. Gantier
9 T LR Agonists as Adjuvants for Cancer Vaccines . . . . . . . . . . . . . . . . . 195
Ji-Kun Li, Jesse J. Balic, Liang Yu, and Brendan Jenkins
vii
viii Contents
10 Telomere Damage Response and Low-Grade Inflammation . . . . . . . 213
Lihui Wang, Xianhua Yu, and Jun-Ping Liu
11 The Development and Diversity of ILCs, NK Cells
and Their Relevance in Health and Diseases . . . . . . . . . . . . . . . . . . . . 225
Yuxia Zhang and Bing Huang
Contributors
Jesse  J.  Balic Centre for Innate Immunity and Infectious Diseases, Hudson
Institute of Medical Research, Clayton, VIC, Australia
Department of Molecular Translational Science, Faculty of Medicine, Nursing and
Health Sciences, Monash University, Clayton, VIC, Australia
Zijuan Chen Department of Immunology, School of Basic Medical Sciences,
Fudan University, Shanghai, People’s Republic of China
Key Laboratory of Medical, Molecular Virology of Ministries of Education and
Health, School of Basic Medical Sciences, Fudan University, Shanghai, People’s
Republic of China
Dominic De Nardo Inflammation Division, The Walter and Eliza Hall Institute of
Medical Research, Parkville, VIC, Australia
Department of Medical Biology, The University of Melbourne, Parkville, Australia
Michael P. Gantier Centre for Innate Immunity and Infectious Diseases, Hudson
Institute of Medical Research, Clayton, VIC, Australia
Department of Molecular and Translational Science, Monash University, Clayton,
VIC, Australia
Doudou Hao Department of Immunology, School of Basic Medical Sciences,
Fudan University, Shanghai, People’s Republic of China
Key Laboratory of Medical, Molecular Virology of Ministries of Education and
Health, School of Basic Medical Sciences, Fudan University, Shanghai, People’s
Republic of China
Yiqun Hu Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai
Jiao Tong University School of Medicine, Shanghai, China
Bing  Huang Guangzhou Institute of Paediatrics, Guangzhou Women and
Children’s Medical Centre, Guangzhou Medical University, Guangzhou,
Guangdong, China
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