[in Japanese]

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Anti β2-GPI antibody is one of antiphospholipid antibody(APA)and this antibody bins to protein (β2-GPI)which binds to phospholipid. Recently many pathogenic mechanism concerning about APA were discovered APAs cause not only intravascular coagulation but also activation of endothelial cells and placental trophoblast. The premature delivery caused by severe preeclampsia,eclampsia and placental dysfunction is included in the criteria of antiphospholipid syndrome. In cases of APS during pregnancy, adequate care and treatment should be done for not only thrombosis but also placental dysfunction relate to villous damage.

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Spermatozoa develop in the testis after that immune tolerance has been established and thus contains autoimmunogenic antigens. However, the testis is known as an immunologically privileged organ. In particular, blood-testis barrier formed by Sertoli cells protects autoimmunogeneic spermatozoa from attack by the self-immune system. In addition, there have been some studies attracting attention about intra-testicular cytokines under normal and pathological conditions. It is known that Epstein-Barr virus-induced gene-3 (EBI3) is one of the common molecules of interleukin 27 and 35 as immunosuppressive cytokines. While initial studies suggested that EBI3 had an important role in promoting cellular immune responses, subsequent studies have revealed that EBI3 receptor signaling influences a variety of immune cell types and can inhibit both cellular and humoral immune responses, but its role in the testis has not yet been available. In the present study, we investigated the intra-testicular EBI3 in the normal mice and analyzed the testes of EBI3-knockout (EBI3KO) mice by using histchemistry and immunohistchemistry. The results showed that the expression of EBI3 in the normal testis was detected on interstitial cell, spermatid and sperm head. In analyses of EBI3KO mice, multinuclear giant cells were observed in the several seminiferous tubules. Moreover, CD4, CD8 and B220 positive cells were detected in testicular interstitium accompanied by appearance of serum autoantibodies against sperm head in EBI3KO mice. Our results indicate that a lack of immunosuppressive EBI3 may affect the testicular microenvironment, resulting in the local autoimmunity.

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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.

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