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Heat shock protein A4L is a potent autoantigen for testicular autoimmunity in mice
Journal of Reproductive Immunology ( IF 3.4 ) Pub Date : 2021-04-01 , DOI: 10.1016/j.jri.2021.103318
Kenta Nagahori 1 , Shuichi Hirai 2 , Naoyuki Hatayama 3 , Miyuki Kuramasu 1 , Takuya Omotehara 1 , Shinichi Kawata 1 , Zhonglian Li 1 , Hidenobu Miyaso 1 , Yuki Ogawa 1 , Ning Qu 4 , Hayato Terayama 4 , Shogo Hayashi 5 , Shuang-Qin Yi 6 , Munekazu Naito 2 , Masahiro Itoh 1
Affiliation  

Experimental autoimmune orchitis (EAO) may be used as a model to investigate immunological infertility in men. Murine EAO is induced via immunization with auto-immunogenic antigens (AIAgs) from testicular germ cells (TGCs). CD4 + T cells play a crucial role in EAO induction. However, whether AIAgs induce an immune response remains unclear. We aimed to identify self-antigens that induce EAO by screening a phage display library of random TGC peptides using IgG from EAO-induced A/J mice. Twenty TGC-specific AIAgs were detected, and G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) and heat shock protein A4L (HSPA4L) were identified as candidate AIAgs that induce EAO. Immunization with GIT1 or HSPA4L, emulsified in complete Freund’s adjuvant, resulted in 66 % or 100 % incidence of EAO, respectively, indicating that HSPA4L is a most potent AIAg that induces EAO in mice. These findings may expectedly help improve the diagnostic procedures and treatment of immunological infertility in men.



中文翻译:

热休克蛋白 A4L 是小鼠睾丸自身免疫的有效自身抗原

实验性自身免疫性睾丸炎 (EAO) 可用作研究男性免疫性不孕症的模型。通过使用来自睾丸生殖细胞 (TGC) 的自身免疫原性抗原 (AIAg) 进行免疫诱导小鼠 EAO。CD4 + T 细胞在 EAO 诱导中起关键作用。然而,AIAgs 是否诱导免疫反应仍不清楚。我们旨在通过使用来自 EAO 诱导的 A/J 小鼠的 IgG 筛选随机 TGC 肽的噬菌体展示文库来鉴定诱导 EAO 的自身抗原。检测到 20 个 TGC 特异性 AIAg,G 蛋白偶联受体激酶 2 相互作用蛋白 1 (GIT1) 和热休克蛋白 A4L (HSPA4L) 被确定为诱导 EAO 的候选 AIAg。用完全弗氏佐剂乳化的 GIT1 或 HSPA4L 进行免疫接种,分别导致 66% 或 100% 的 EAO 发生率,表明 HSPA4L 是一种最有效的 AIAg,可在小鼠中诱导 EAO。这些发现可能有助于改进男性免疫性不孕症的诊断程序和治疗。

更新日期:2021-04-21
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