Epstein-Barr virus-Induced gene-3(EBI3)knockoutマウスにおける 精巣内免疫微小環境の変化  [in Japanese] Testicular immune-microenvironment in the Epstein-Barr virus-Induced gene-3 (EBI3) knock out mice  [in Japanese]

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Haploid germ cells (=精子細胞・精子)は,様々な自己抗原を含んでいる。これら自己抗原はSertoli細胞間の結合で構成される血液-精巣関門(blood-testis barrier=BTB)によって免疫系からある程度護られているとされている。また,精巣内で分泌されるサイトカインが免疫学的抑制環境と関係しているという報告もある。最近,免疫抑制効果を示すサイトカインとして新たにIL27やIL35が同定され,その共通分子であるEpstein-Barr virus-Induced gene-3(EBI3)のknockoutマウスにおいて,様々な自己免疫疾患の病態増悪を認めることが報告されている。しかしながら,精巣においてEBI3に関する報告は未だない。本研究では12週齢雄C57BL/6マウスにおいて精巣内のEBI3発現を調べると共にEBI3を欠損させること(EBI3KO)によって精巣免疫微小環境にどのような影響を及ぼすかを検討した。その結果,正常マウスの精巣内では,EBI3発現は間質細胞および精子細胞・精子の頭部に検出された。EBI3KOマウスの解析では,精細管中に多核巨細胞の増加や間質中にCD4,CD8,B220陽性細胞の浸潤が認められた。さらに,精子細胞・精子に対する自己抗体が血清中に認められた。EBI3は精巣微小環境において免疫学的抑制機構の形成や維持に関わっている可能性が示唆された。

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.


  • Reproductive Immunology and Biology

    Reproductive Immunology and Biology 28(0), 19-25, 2013

    Japan Society for Immunology of Reproduction


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