Heat shock protein A4L is a potent autoantigen for testicular autoimmunity in mice. (June 2021)

• Record Type: Journal Article
• Authors: Nagahori, Kenta; Hirai, Shuichi; Hatayama, Naoyuki; Kuramasu, Miyuki; Omotehara, Takuya; Kawata, Shinichi; Li, Zhonglian; Miyaso, Hidenobu; Ogawa, Yuki; Qu, Ning; Terayama, Hayato; Hayashi, Shogo; Yi, Shuang-Qin; Naito, Munekazu; Itoh, Masahiro
• Is Part Of: Journal of reproductive immunology. Volume 140(2020)
• Publication Date: 2021-06
• Subjects: AIAg Autoimmunogenic antigen -- BP Bordetella pertussis -- BTB Blood–testis barrier -- CFA Complete Freund's adjuvant -- DAB 3, 3′-diaminobenzidine -- DAZAP1 DAZ-associated protein 1 -- EAE Experimental autoimmune encephalomyelitis -- EAO Experimental autoimmune orchitis -- EAU Experimental autoimmune uveoretinitis -- ES Epididymal spermatozoa -- GIT1 G protein-coupled receptor kinase 2 interacting protein-1 -- HBSS Hank's balanced salt solution -- HEK293T Human embryonic kidney 293T -- HRP horseradish peroxidase -- HSC70T Heat shock protein 1-like -- HSP Heat shock protein -- HSPA4L Heat shock protein A4L -- OPD o-phenylenediamine dihydrochloride -- ORP150 150-kDa oxygen-regulated protein -- RPMI1640 Roswell Park Memorial Institute medium 1640 -- TGC Testicular germ cell; Autoimmune orchitis -- Male infertility -- Aspermatogenesis -- Testicular dysfunction -- Autoimmunogenic antigen; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2021.103318
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: Immunization with testicular germ cells (TGC) induces experimental autoimmune orchitis (EAO). HSPA4L, a purified TGC protein, was found to be a strong EAO inducer. HSPA4L could be a target and a useful biomarker of EAO. Abstract: 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.