Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
34
1
2014
Changes in Adipose Tissue Macrophages and T Cells During Aging
1-14
10.1615/CritRevImmunol.2013006833
Sanjay K.
Garg
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan
Colin
Delaney
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan
Hang
Shi
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan
Raymond
Yung
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan
adipose tissue
macrophage
lymphocytes
inflammation
aging
Adipose tissue historically was believed to be an inert tissue, functioning primarily in the storage of
energy and thermal homeostasis. However, recent discoveries point toward a critical role for adipocytes in endocrine
function as well as immune regulation. Excess body fat, accumulated through aging and/or a calorie-rich diet, is
associated with many chronic metabolic and inflammatory diseases. Within the stromal vascular fraction of adipose
tissue, macrophages and T cells accumulate with increasing tissue mass, secreting pro- or anti-inflammatory cytokines.
In this review we discuss the current understanding of immune cell function in both diet-induced and age-related
obesity. In both models of obesity, the classically activated, pro-inflammatory (M1) subtype takes precedence over the
alternatively activated, anti-inflammatory (M2) macrophages, causing tissue necrosis and releasing pro-inflammatory
cytokines like interleukin-6. Other distinct adipose tissue macrophage subtypes have been identified by surface
marker expression and their functions characterized. Adipose tissue T cell recruitment to adipose tissue is also different
between aging- and diet-induced obesity. Under both conditions, T cells exhibit restricted T-cell receptor
diversity and produce higher levels of pro-inflammatory signals like interferon-γ and granzyme B relative to young or healthy mice. However, numbers of regulatory T cells are dramatically different between the 2 models of obesity.
Taken together, these findings suggest models of age- and diet-induced obesity may be more distinct than previously
thought, with many questions yet to be resolved in this multidimensional disease.
T-Cell Immunity to Influenza A Viruses
15-39
10.1615/CritRevImmunol.2013010019
Emma J.
Grant
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia
Li
Chen
Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, Chongqing, PR China; Department of Biochemistry, La Trobe University, Bundoora, Australia
Sergio
Quinones-Parra
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia
Ken
Pang
Inflammation Division, The Walter and Eliza Hall Institute for Medical Research, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia
Katherine
Kedzierska
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia
Weisan
Chen
Department of Biochemistry, La Trobe University, Bundoora, Australia
influenza
T cell
epitope
HLA
vaccine
Influenza infection remains a global threat to human health. Influenza viruses are normally controlled
by antibodies specific for the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Standard influenza vaccines are aimed at inducing these antibodies, but they must be administered annually and can be rendered
ineffective since different strains circulate from year to year and vary considerably in their individual HA and NA
profiles. Influenza-specific T cells have been shown to be protective in animal models and typically recognize the
more conserved internal influenza proteins. Improving our understanding of influenza-specific T-cell responses,
including immunodominance, specific epitope sequences, strain-related epitope variation, host/virus interaction, and the balance between immunity versus immunopathology, will be important to improve future T-cell-based vaccines,
which promise broader strain coverage and longer-lasting protection than current standard vaccines.
The Inflammasome and Its Regulation
41-80
10.1615/CritRevImmunol.2013008686
Kohsuke
Tsuchiya
Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida konoe-cho, Sakyo-ku, Kyoto, Japan
Hideki
Hara
Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida konoe-cho, Sakyo-ku, Kyoto, Japan
ASC speck
pyroptosome
NLRP3
caspase-1
mitochondria
nitric oxide
Inflammasomes, multiprotein platforms of caspase-1 activation, are assembled in response to a number of exogenous and endogenous danger signals, leading to the production of pro-inflammatory cytokines and induction of inflammatory cell death through the activation of caspase-1. Inflammasomes have been implicated in a wide range of physiological and pathological processes, including host defense against microbial pathogens, maintenance of intestinal homeostasis, and even development of inflammatory disorders. Thus, inflammasomes can
be both beneficial and detrimental, and understanding the mechanisms involved in inflammasome activation may
provide a better approach to prevent the harmful effects of the inflammatory response. Although inflammasome
complexes are formed via protein-protein interactions between their components, accumulating evidence suggests
that inflammasome activation is positively and negatively regulated by ligand-binding receptors, accessory proteins,
other caspases, cytokines, kinases/phosphatases, redox sensors, ion homeostasis, second messengers, organelles, cytoskeleton, and autophagy, among others. Moreover, inflammasome activation can result in the formation of another caspase-1-activating protein complex, the ASC speck/pyroptosome, which is also tightly controlled. In this review, we discuss how the assembly of inflammasomes and ASC speck is regulated by complex mechanisms. Recent findings
on effector functions and biological roles of inflammasomes also are summarized.
iNKT Cells: Innate Lymphocytes with a Diverse Response
81-90
10.1615/CritRevImmunol.2014010088
Marta
Monteiro
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
Luis
Graca
Instituto Gulbenkian de Ciência, Oeiras, Portugal
natural killer T cells
cytokines
T-cell receptor
a-galactosylcermide
naive
effector
memory
plasticity
Foxp3
IL-17
It is now established that natural killer T (NKT) cells can influence adaptive immune responses by producing vast amounts of cytokines. Different subsets of NKT cells with distinctive functional characteristics regarding cytokine production have been described. This is the case for NKT1, NKT2, or NKT17 that resemble conventional CD4 Th1, Th2, and Th17 cells in the cytokines they produce. Unlike conventional CD4 T cells that mostly acquire functional specialization in the periphery, a number of NKT cells become specialized effectors during thymic development. This opinion article describes the evidence for an extrathymic commitment of specialized NKT-cell subsets that, together with thymic lineages, contributes to the overall functional diversity of NKT cells participating in immune responses in the periphery.