妊娠マウスにおける樹状細胞亜分画変動とIL-12産生

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Dendritic cells (DCs) play a crucial role in providing an appropriate immune balance during pregnancy. It has recently been reported that two distinct types of DCs are arranged in the murine system. One subtype is the DCs bearing the C-type lectin CD205 (DEC-205) having the capacity to establish Th1 polarization. The other is the DCs expressing 33D1, recognizing DC inhibitory receptor-2 (DCIR-2), having the capacity to induce Th2 polarization. In addition, we found that the balance of DC subtypes was affected mainly by progesterone, which induced a dose-dependent reduction of the DEC-205/33D1 ratio together with/without a stable amount of estrogen(1). The DEC-205/33D1 ratio decreased gradually with the progress of pregnancy and rapid augmentation of this ratio was seen around delivery period. Here, we demonstrated that the fetal loss could be induced by the depletion of 33D1+ DCs during perinatal period mediated through the transient IL-12 secretion, and pre-administration of progesterone could rescue this fetal loss. Similar miscarriages were also observed when pregnant mice were intraperitoneally (i.p.) injected twice with IL-12 on Gd 9.5 and 10.5. Moreover, prior inoculation of progesterone suppressed the enhanced serum IL-12 production in mice treated with 33D1 antibody, indicating that progesterone might inhibit temporal IL-12 secretion around Gd 10.5 and thus miscarriage was prevented. These findings suggest that the balance of DC subsets is crucial for maintaining pregnancy and we can prevent miscarriage by manipulating the activity of the DC subpopulation of pregnant individuals by progesterone administration.

妊娠マウスにおける樹状細胞亜分画変動とIL-12産生

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