Disruption of maternal immune balance maintained by innate DC subsets results in spontaneous pregnancy loss in mice

Negishi, Yasuyuki; Wakabayashi, Ayako; Shimizu, Mitsuru; Ichikawa, Tomoko; Kumagai, Yoshihiro; Takeshita, Toshiyuki; Takahashi, Hidemi

doi:10.1016/j.imbio.2012.01.011

Cited by 32 publications

(34 citation statements)

References 31 publications

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“…These findings show the importance of balancing DC subsets during pregnancy. Interestingly, progesterone could rescue the abortions, highlighting the role of hormones in the balance of the pregnancy immune response (57). …”

Section: Dendritic Cellsmentioning

confidence: 99%

Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation

Zenclussen

Hämmerling

2015

Front. Immunol.

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Implantation of the fertilized egg into the maternal uterus is a crucial step in pregnancy establishment. Increasing evidence suggests that its success depends on various cell types of the innate immune system and on the fine balance between inflammatory and anti-inflammatory processes. In addition, it has recently been established that regulatory T cells play a superordinate role in dictating the quality of uterine environment required for successful pregnancy. Here, we discuss the cellular regulation of uterine receptivity with emphasis on the function and regulation of cells from the innate and adaptive immune system.

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Section: Dendritic Cellsmentioning

confidence: 99%

Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation

Zenclussen

Hämmerling

2015

Front. Immunol.

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“…We recently reported that 33D1+ DCs can be depleted in vivo by treating C57BL/6 mice with an anti-33D1 mAb and that the Th1/Th2 balance can be controlled by the manipulation of DC subsets [8,9]. To observe the effects of 33D1+ DC depletion in AR mice, we first confirmed whether 33D1+ DCs could also be depleted in normal BALB/c mice using this procedure.…”

Section: Resultsmentioning

confidence: 75%

“…Indeed, we have recently reported that the number of 33D1+ DCs increases to maintain Th2 dominance during pregnancy [9], while such dominance appears to be completely abrogated after delivery. Thus, the internal immune balance is shifted towards a Th1 response to improve the allergic status.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, we have previously shown that it is possible to deplete 33D1+ DCs and establish Th1 dominance by DEC-205+ DCs through the administration of a 33D1-specific monoclonal antibody (mAb) in vivo [8]. Based on these findings, we recently reported that the depletion of 33D1+ DCs in pregnant mice following syngeneic mating strongly induced spontaneous abortion during the perinatal period that was mediated through Th1 augmentation initiated by DEC-205+ DC dominance [9]. In contrast, Th2 dominance organized by the 33D1+ DC subset may be required to maintain a successful pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model

Murakami¹,

Nakagawa²,

Shimizu³

et al. 2015

Int Arch Allergy Immunol

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Background: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). Methods: Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. Results: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion. Conclusions: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo.

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“…Accumulating evidence indicates that dendritic cells (DCs) (9)(10)(11)(12) and regulatory T cells (Tregs) (13)(14)(15) are crucial for the establishment and maintenance of pregnancy. For instance, Plaks et al (10) demonstrated that the depletion of DCs causes a failure of embryo implantation in mice, and the depletion of Tregs induces implantation failure and increases resorption in allogeneic, but not in syngeneic, mice (14).…”

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confidence: 99%

Oil-Soluble Contrast Medium (OSCM) for Hysterosalpingography Modulates Dendritic Cell and Regulatory T Cell Profiles in the Peritoneal Cavity: A Possible Mechanism by Which OSCM Enhances Fertility

Izumi

Koga

Takamura

et al. 2017

The Journal of Immunology

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Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) is known to enhance fertility, although the mechanism is unclear. OSCM remains in the peritoneal cavity for several months after HSG. We hypothesized that OSCM that remains in the peritoneal cavity modulates dendritic cell (DC) and regulatory T cell (Treg) profiles and contributes to enhanced fertility. We characterized the profiles of DCs and Tregs in the peritoneal fluid from women who had undergone HSG. In vitro and in vivo effects of OSCM on monocyte-derived DCs and mouse peritoneal T cells were also evaluated. In comparison with women who have never experienced HSG, samples from women who had undergone HSG contained myeloid DCs with greater complexity and maturation, as well as had a marginally greater proportion of Tregs in their peritoneal fluid. OSCM is incorporated by monocyte-derived DCs, which causes their maturation and contributes to the increase in Treg proportions. Samples from OSCM-injected mice contained greater proportions of Tregs in comparison with controls. These studies demonstrate that OSCM modulates T cell profiles that are compatible with the condition observed in women who have undergone HSG. This study demonstrates that exogenous lipids administered to the peritoneal cavity are incorporated by DCs and that they significantly alter the immune environment in the peritoneal cavity. This immunological impact may contribute to enhanced fertility and the development of alternative therapeutic strategies for managing other pathological conditions associated with immunological abnormalities in the peritoneal cavity.

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Disruption of maternal immune balance maintained by innate DC subsets results in spontaneous pregnancy loss in mice

Cited by 32 publications

References 31 publications

Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation

Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation

Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model

Oil-Soluble Contrast Medium (OSCM) for Hysterosalpingography Modulates Dendritic Cell and Regulatory T Cell Profiles in the Peritoneal Cavity: A Possible Mechanism by Which OSCM Enhances Fertility

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