ArticleThe Journal of clinical investigation2017
Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 146 citations in OpenAlex.
- Immunological dynamics of the epididymis: from experimental insights to clinical translation.Reproduction & fertility · 2026Review
- Common Environmental Hazards and Male Infertility: Effects on Epididymal Immune Microenvironment.Toxics · 2026Review
- The Role of Cytokines in the Development and Functioning of the Hypothalamic-Pituitary-Gonadal Axis in Mammals in Normal and Pathological Conditions.International journal of molecular sciences · 2025Review
- Chronic inflammation drives epididymal tertiary lymphoid structure formation and autoimmune fertility disorders in mice.Nature communications · 2025Article
- Human embryonic stem cell-derived Sertoli cells as an immune modulator of cell transplantation therapy in a diabetic mice model.Stem cell research & therapy · 2025Article
- Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice.Current issues in molecular biology · 2025Article
- Immune Microenvironment Dysregulation: A Contributing Factor to Obesity-Associated Male Infertility.Biomedicines · 2025Review
- Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor.Communications biology · 2025Article
- Galectin-1 and galectin-3 in male reproduction - impact in health and disease.Seminars in immunopathology · 2025Review
- Immune Regulation in the Testis and Epididymis.Advances in experimental medicine and biology · 2025Review
- Sertoli cells as a hub in testicular development and male reproductive.Frontiers in cell and developmental biology · 2025Review
- Extracellular Vesicles in the Aging Male Reproductive System: Progresses and Perspectives.Advances in experimental medicine and biology · 2025Review
- A Comprehensive Bibliometric Analysis of Orchitis Research from 1980 to 2023.Advances in experimental medicine and biology · 2025Review
- Testicular immunity.Molecular aspects of medicine · 2024Review
- 9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation.Reproductive biology and endocrinology : RB&E · 2024Article
- The mouse epididymal amyloid matrix is a mammalian counterpart of a bacterial biofilm.iScience · 2024Article
- Impaired Spermatogenesis in Infertile Patients with Orchitis and Experimental Autoimmune Orchitis in Rats.Biology · 2024Article
- Regulatory T cells play a crucial role in maintaining sperm tolerance and male fertility.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Sequence level genome-wide associations for bull production and fertility traits in tropically adapted bulls.BMC genomics · 2023Article
- Prophylactic and therapeutic vaccination protects sperm health from Chlamydia muridarum-induced abnormalities.Biology of reproduction · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered. Nonsequestered MCGA (NS-MGCA) egressed from normal tubules, as evidenced by their ability to interact with systemically injected antibodies and form localized immune complexes outside the Sertoli cell barrier. NS-MGCA derived from cell fragments that were discarded by spermatids during spermiation. They egressed as cargo in residual bodies and maintained Treg-dependent physiological tolerance. In contrast, sequestered MGCA (S-MGCA) were undetectable in residual bodies and were nontolerogenic. Unlike postvasectomy autoantibodies, which have been shown to mainly target S-MGCA, autoantibodies produced by normal mice with transient Treg depletion that developed autoimmune orchitis exclusively targeted NS-MGCA. We conclude that spermiation, a physiological checkpoint in spermatogenesis, determines the egress and tolerogenicity of MGCA. Our findings will affect target antigen selection in testis and sperm autoimmunity and the immune responses to CTA in male cancer patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.