|
Current
Immunology Reviews
ISSN: 1573-3955
Current Immunology Reviews
Volume 4, Number 3, August 2008
Contents
Identification of New Susceptibility Genes for Type
1 Pp. 166-133
Diabetes: An Update Dimitry A. Chistiakov,
Natalia V. Voronova and Emma I. Chistiakova
[Abstract]
The Regulation of Neuroimmune-Endocrine
Interactions: Mechanisms, Molecular Pathways Unraveled and
the Pivotal Role of Cytokines – A Unsung Putative Bidirectional
Interdependence between the Immune and Neuroendocrine Interfaces
Pp. 134-158
John J. Haddad
[Abstract]
Expression and Function of Angiomodulating
Cytokines in Rheumatoid Arthritis and Experimental Arthritis:
Important Therapeutic Targets Pp. 159-167
Tsuyoshi Kasama, Kuninobu Wakabayashi, Tsuyoshi Odai and
Takeo Isozaki
[Abstract]
Toll-Like Receptor System in the Human
Endometrium Pp. 168-175
Kaei Nasu, Akitoshi Yuge, Akitoshi Tsuno and Hisashi
Narahara
[Abstract]
Antibodies Against Muscarinic Receptors
in Breast Cancer: Agonizing Tumor Growth Pp.
176-182
Gabriel L. Fiszman and María
E. Sales
[Abstract]
Abstracts
[Back to top]
Identification of New Susceptibility Genes
for Type 1
Diabetes: An Update Dimitry A. Chistiakov,
Natalia V. Voronova and Emma I. Chistiakova
With a relative failing of linkage and candidate gene
association studies, there has been much sceptism about the
ability of geneticists to identify genes for common, complex
disorders. In the field of the genetics of type 1 diabetes
(T1D), more than twenty years of labor-intensive and cost-expensive
effort has resulted in the identification of only four T1D-
predisposing loci, which are as follows: Human Leucocyte Antigens
(HLA) class II, insulin gene region, cytotoxic T-lymphocyte
associated 4 (CTLA-4), and protein tyrosine phosphatase, non-receptor
member 22 (PTPN22). Recent technological advances and a better
understanding of the genetic architecture of complex diseases
has led to the development of the genome-wide association
(GWA) study, which is a powerful new approach to identifying
genes influencing predisposition to common, complex disease.
For T1D, the implication of the GWA approach in 2005 resulted
in rapid progress in the discovery of new etiological variants.
To date, the involvement in T1D pathogenesis is proven for
several new genes such as interleukin 2 receptor alpha (IL2RA/CD25),
interferon-induced helicase domain 1 (IFIH1), and small ubiquitin-related
modifier 4 (SUMO4). An extended list of likely candidates
for T1D susceptibility identified through the GWA approach
includes PTPN2, CD226, PPARG2, IL2/IL21, ADAM33, and some
other genes. A great benefit to clinical medicine is expected
in the years to come, and whilst prediction of disease and
pharmacogenetics may eventually prove valuable, the greatest
clinical benefit of GWA studies is likely to come from etiological
insights into disease processes.
[Back to top]
The Regulation of Neuroimmune-Endocrine Interactions: Mechanisms,
Molecular Pathways Unraveled and the Pivotal Role of Cytokines
– A Unsung Putative Bidirectional Interdependence between
the Immune and Neuroendocrine Interfaces
John J. Haddad
With research continuing apace, significant bidirectional
interdependence between the immune system and the central
nervous system (CNS) has been demonstrated, with the intervention
of common messengers, cofactors and biological response modifiers.
Cytokines, or biologic response modifiers, peptide hormones
and neurotransmitters, as well as their receptors/ligands,
are endogenous to the brain, endocrine and immune systems.
These shared ligands and receptors are used as a common chemical
language for communication within and between the immune and
neuroendocrine systems. Such communication suggests an immunoregulatory
role for the brain, on one hand, and a sensory function for
the immune system, on the other hand. Furthermore, interplay
between the immune, nervous and endocrine systems, so commonly
known as the ‘trio’ complex, is most
commonly associated with the pronounced effects of stress
and stress-related conditions on immunity. The cytokines and
related cofactors of the immune system are thus capable of
modulating responses and certain processes in the CNS, while
neuropeptides and neurotransmitters can exert their effects
over cellular groups in the immune system. One way in the
neuroimmunological system is controlled by the hypothalamic-pituitary-adrenals
(HPA)-axis, a major coordinator and regulator of interaction
among the immune, CNS and endocrine systems. The HPA axis
is, therefore, the key player in stress responses; it is well
established that both external and internal stressors activate
the HPA axis. Cytokines, or immunotransmitters, are those
chemical messengers that stimulate the HPA axis when the body
is under stress or experiencing an infection. Neuroimmune
interactions are essential to unravel vital communications
between the immune and nervous systems in such a manner this
crosstalk remains a cornerstone in maintaining and perpetuating
a stance of homeostasis. It is the subject of this synopsis
to tackle the issue of neuroimmune interactions, their pathways
and mechanisms of action, and their relevance to physiologic
and pathophysiologic arenas.
[Back to top]
Expression and Function of Angiomodulating Cytokines in Rheumatoid
Arthritis and Experimental Arthritis: Important Therapeutic
Targets
Tsuyoshi Kasama, Kuninobu Wakabayashi, Tsuyoshi Odai and
Takeo Isozaki
The progression of synovial inflammation and joint destruction
in rheumatoid arthritis (RA) is characterized by a pronounced
tumor-like expansion of the synovium. Neovascularization,
which may play a pivotal role in the physiological and pathological
condition, is a complex process involving endothelial cell
division, selective degradation of vascular basement membranes
and the surrounding extracellular matrix, and endothelial
cell migration. The involvement of several endogenous molecules
has been purported based on the ability of these molecules
to regulate the proliferation of endothelial cells. Moreover,
a number of factors which regulate both angiogenic and angiostatic
functions may be crucial in promoting neovascularisation.
These include vascular endothelial growth factor (VEGF), fibroblast
growth factor (FGF), angiopoietins and chemokine family such
as CXCL8 and CXCL10. This review will discuss the expression
and regulation of these angiogenic and angiostatic cytokines
in the context of chronic inflammatory arthritis such as RA
and experimental arthritis.
[Back to top]
Toll-Like Receptor System in the Human Endometrium
Kaei Nasu, Akitoshi Yuge, Akitoshi Tsuno and Hisashi
Narahara
The mucosal surface of the uterine cavity is a complex biosystem,
which provides a barrier against the outside world and participates
in both innate and acquired immune defense systems. This mucosal
compartment has adapted to a dynamic, non-sterile environment
challenged by a variety of antigenic/inflammatory stimuli
associated with sexual intercourse and endogenous vaginal
microbiota. Thus, the epithelial cells, fibroblasts, lymphocytes,
macrophages, and dendritic cells associated with the human
endometrium possess unique features that enable them to adapt
to this dynamic milieu. Rapid innate immune defenses against
microbial infection usually involve the recognition of invading
pathogens by specific pattern-recognition receptors recently
attributed to the family of Toll-like receptors (TLRs). TLRs
recognize conserved pathogen-associated molecular patterns
(PAMPs) synthesized by microorganisms, but not by the host.
Members of the TLR family, which includes 10 human TLRs identified
to date, recognize distinct PAMPs produced by various bacterial,
fungal, and viral pathogens. The available literature regarding
the innate immune system of the endometrium during human reproductive
processes was reviewed in order to identify studies specifically
related to the expression and function of TLRs under normal
as well as pathological conditions. Increased understanding
of these molecules in the endometrium may provide insight
into site-specific immunoregulatory mechanisms in the female
reproductive tract.
[Back to top]
Antibodies Against Muscarinic Receptors in Breast Cancer:
176 Agonizing Tumor Growth
Gabriel L. Fiszman and María
E. Sales
In developed countries, cancer has replaced infectious diseases
as a major cause of death. Currently, efforts in the immunoprevention
of cancer are beginning to resemble that presented by the
prevention of infectious diseases by immunization a century
ago. Breast cancer is the most frequent type of tumor in women
and is the first cause of death by this illness, among them.
Moreover, cancer incidence will grow during next years.
Some findings in autoimmunity related to breast cancer in
animal models have been important to clarify mechanisms that
potentiate tumor growth. Clinical and experimental data now
clearly indicate that chronic inflammation significantly contributes
to cancer development. Emerging out of these studies is an
appreciation that persistent humoral immune responses exacerbate
recruitment and activation of innate immune cells in neoplastic
microenvironment where they regulate tissue remodeling, pro-angiogenic
and pro-survival pathways that together potentiate cancer
development. Generally, antigens involved in autoimmune response
in breast cancer are modified self-proteins or over-expressed
normal proteins that induce autoantibodies (autoAbs) formation
which exhibit tumor promoting actions. This article will review
recent results concerning to the ability of muscarinic acetylcholine
receptors (mAChR) expressed in transformed cells, to trigger
autoAbs formation either in experimental models or in breast
cancer patients. We will also discuss the action of these
antibodies as agonists in mAChR functions.
|
