Intercellular Adhesion Molecule-1/LFA-1 Cross Talk Is a Proximate Mediator Capable of Disrupting Immune Integration and Tolerance Mechanism at the Feto-Maternal Interface in Murine Pregnancies

Blois, Sandra M.; Tometten, Mareike; Kandil, Judith; Hagen, Edward H.; Klapp, Burghard F.; Margni, Ricardo A.; Arck, Petra C.

doi:10.4049/jimmunol.174.4.1820

Cited by 90 publications

(95 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treg cells are known to mediate maternal tolerance through IL-10 (56), which decreased significantly in specimens from spontaneous abortion (57). Furthermore, uterine DC from mice with high abortion rates displayed decreased expression of IL-10 compared with that from mice with a low incidence of fetal rejection (58). Alternatively, activated macrophages or M2 macrophages also exert an immunosuppressive phenotype via the production of IL-10 and indoleamine 2,3-dioxygenase activity (59).…”

Section: Discussionmentioning

confidence: 99%

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Sun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

257

218

View full text Add to dashboard Cite

Natural killer (NK) cells accumulate at the maternal-fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that T H 17 cells and local inflammation can occur at the maternal-fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory T H 17 cells via IFN-γ secreted by the CD56 bright CD27 + NK subset. This NK-cell-mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T H 17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal-fetal interface by suppressing T H 17-mediated local inflammation.regulatory NK cells | fetomaternal tolerance D uring pregnancy, allogeneic fetal cells invade the maternal decidua but they are protected from the maternal immune system. This invasion of extraembryonic trophoblasts does not harm gestation during normal pregnancy; it establishes tolerance at the maternal-fetal interface (1), (2), although the mechanism of such tolerance is not clear. In addition, inflammatory responses induced by a variety of mechanisms can result in embryo loss, but mild inflammation can be effectively controlled through regulatory mechanisms to maintain successful pregnancy (3). Thus, suppression of strong inflammatory responses is essential to ensure normal pregnancy (4, 5), although the mechanisms involved in regulating local inflammation without compromising overall maternal immunity during a successful pregnancy remain unknown.Multiple mechanisms are potentially involved in promoting immune tolerance during pregnancy. For example, T H 2 cytokine polarization (6-9), the expression of the Fas ligand on trophoblast cells (10), and the inhibition of complement activation (11) are crucial for ensuring tolerance at the maternal-fetal interface. In addition, a delicate balance exists between inhibitory (PD-L1, Stat3, and TGF-β1) and stimulatory (CD80 and CD86) signals during the establishment of immune privilege (12-18). Furthermore, studies have shown that galectin-1 (19) and indoleamine 2,3-dioxygenase (20) play pivotal roles in maternal-fetal tolerance. Several types of immune cells, such as CD4 + CD25 + regulatory T cells, are also essential in the generation of maternal-fetal tolerance in mice and humans (7,(21)(22)(23)(24). Furthermore, natural killer (NK) T cells and immature dendritic cells have been reported to promote the expansion of Treg cells that confer protection of the fetus (19).Despite considerable progress, many questions remain unanswered. The most striking feature at the maternal-fetal interface is the accumulation of NK cells, which account for ∼60-90% of immune cells in the decidua in humans during early pregnancy (25)(26)(27)(28)(29) and a...

show abstract

Section: Discussionmentioning

confidence: 99%

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Sun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

257

218

View full text Add to dashboard Cite

show abstract

“…In this study, two well-characterized experimental models were combined: first, the exposure to sound stress during pregnancy, which has been shown to constitute a challenge to fetal tolerance if exposure to stress is performed during the peri-implantation period (22). Because teratogenesis had to be avoided and a vulnerable window for fetal lung development and immune system programming is likely present later in gestation (27), we changed the stress intervention time point during gestation from the peri-implantation period to the postimplantation period.…”

Section: Establishment Of a Mouse Model On Fetal Programming Of Allermentioning

confidence: 99%

“…Flow cytometry was performed using our standard protocol (22). Briefly, lung cells were washed twice with buffer (PBS supplemented with 1% BSA; Sigma-Aldrich and 0.1% sodium acid; Sigma-Aldrich).…”

Section: Flow Cytometrymentioning

confidence: 99%

Prenatal Stress Enhances Susceptibility of Murine Adult Offspring toward Airway Inflammation

Pincus-Knackstedt

Joachim²,

Blois³

et al. 2006

The Journal of Immunology

Self Cite

127

View full text Add to dashboard Cite

Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.

show abstract

“…Using a single exposure, effects of stress challenge on the immune response will diminish after 48 hours. 23 …”

Section: Exposure To Stressmentioning

confidence: 99%

“…21,22 Blocking of LFA-1/ICAM-1 in mice in vivo can abrogate the onset of inflammation, hereby preventing fetal rejection. 23 Moreover, LFA-1/ICAM-1 interactions also are important during graft-versus-host reactions, 24 the development of autoimmunity, 25 and neuropeptide SP-induced leukocyte migration. 26 The latter observation is particularly striking since we were recently able to show that stress leads to neurogenic inflammation in murine skin, comprised of sprouting nerve fibers, increased number and activation of MHC II ϩ APCs and mast cells, upregulation of nerve growth factor, and the neuronal plasticity of dorsal root ganglia toward an increased presence of SP ϩ neurons.…”

mentioning

confidence: 99%

Stress-Induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells Towards Maturation and Migration

Joachim

Handjiski

Blois

et al. 2008

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

The skin continuously serves as a biosensor of multiple exogenous stressors and integrates the resulting responses with an individual's central and peripheral endogenous response systems to perceived stress; it also acts to protect against external challenges such as wounding and infection. We have previously shown in mice that stress induces nerve growth factor-and substance P-dependent neurogenic inflammation, which includes the prominent clustering of MHC class II ؉ cells. Because the contribution of dendritic cells (DCs) in response to stress is not well understood, we examined the role of DCs in neurogenic inflammation in murine skin using a well-established murine stress model. We show that sound stress increases the number of intradermal langerin Mammalian skin serves as a complex biological interface system that protects against external challenges such as wounding, infection, or UV radiation and even safeguards against viral and carcinogen-induced transformation. These complex functions only can be executed because skin represents far more than a simple mechanical barrier. It also constitutes a critical first barrier of immune defenses targeted against external stressors that crucially directs the linkage of innate and adaptive immunity. 1 Superimposed on this is the impact of psychological stress, which may challenge these complex interface functions of the skin.2 In this context, we previously introduced the existence of the brain-skin connection 3 by revealing that the skin and its appendages are not only vulnerable to key stress mediators such as Corticotropinreleasing hormone, substance P (SP), and nerve growth factor, but also are themselves potent sources of these stress response mediators. 4 -6 This-insufficiently defined-brain-skin connection provides the rationale for common skin responses to stress such as excessive Supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; grants Ar 232/14-2 and Pa 345/11-2) and the Charité (UFF 99-648 and habilitation programs to R.A.J. and S.M.B.).

show abstract

Intercellular Adhesion Molecule-1/LFA-1 Cross Talk Is a Proximate Mediator Capable of Disrupting Immune Integration and Tolerance Mechanism at the Feto-Maternal Interface in Murine Pregnancies

Cited by 90 publications

References 60 publications

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Prenatal Stress Enhances Susceptibility of Murine Adult Offspring toward Airway Inflammation

Stress-Induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells Towards Maturation and Migration

Contact Info

Product

Resources

About

Intercellular Adhesion Molecule-1/LFA-1 Cross Talk Is a Proximate Mediator Capable of Disrupting Immune Integration and Tolerance Mechanism at the Feto-Maternal Interface in Murine Pregnancies

Cited by 90 publications

References 60 publications

Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal–fetal interface

Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal–fetal interface

Prenatal Stress Enhances Susceptibility of Murine Adult Offspring toward Airway Inflammation

Stress-Induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells Towards Maturation and Migration

Contact Info

Product

Resources

About

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface