Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor
Abstract Tight junctions (TJs) between adjacent Sertoli cells are believed to form immunological barriers that protect spermatogenic cells expressing autoantigens from autoimmune responses. However, there is no direct evidence that Sertoli cell TJs (SCTJs) do indeed form immunological barriers. Here...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07592-0 |
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| author | Taichi Sugawara Kayoko Sonoda Nattapran Chompusri Kazuhiro Noguchi Seiji Okada Mikio Furuse Tomohiko Wakayama |
| author_facet | Taichi Sugawara Kayoko Sonoda Nattapran Chompusri Kazuhiro Noguchi Seiji Okada Mikio Furuse Tomohiko Wakayama |
| author_sort | Taichi Sugawara |
| collection | DOAJ |
| description | Abstract Tight junctions (TJs) between adjacent Sertoli cells are believed to form immunological barriers that protect spermatogenic cells expressing autoantigens from autoimmune responses. However, there is no direct evidence that Sertoli cell TJs (SCTJs) do indeed form immunological barriers. Here, we analyzed male mice lacking claudin-11 (Cldn11), which encodes a SCTJ component, and found autoantibodies against antigens of spermatocytes/spermatids in their sera. Defective spermatogenesis in Cldn11-deficient mice was not restored on a recombination activating gene 2 (Rag2) knockout background lacking mature T and B lymphocytes. This suggests that adaptive immune responses to spermatogenic cells are not a cause of defective spermatogenesis in Cldn11-deficient mice. Further analyses showed that Cldn11 knockout impaired Sertoli cell polarization, localization of stem cell factor (SCF) (a key molecule for maintaining differentiating spermatogonia) to the basal compartment of seminiferous tubules, and also proliferation of differentiating spermatogonia. We propose that CLDN11 creates a microenvironment for SCF-mediated spermatogonial proliferation at the basal compartment via Sertoli cell polarization. |
| format | Article |
| id | doaj-art-636c47a7748747cd8c27a81f4f660811 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-636c47a7748747cd8c27a81f4f6608112025-02-02T12:37:16ZengNature PortfolioCommunications Biology2399-36422025-01-018111610.1038/s42003-025-07592-0Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factorTaichi Sugawara0Kayoko Sonoda1Nattapran Chompusri2Kazuhiro Noguchi3Seiji Okada4Mikio Furuse5Tomohiko Wakayama6Department of Histology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Histology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Histology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Histology, Graduate School of Medical Sciences, Kumamoto UniversityDivision of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto UniversityDivision of Cell Structure, National Institute for Physiological Sciences, National Institute of Natural SciencesDepartment of Histology, Graduate School of Medical Sciences, Kumamoto UniversityAbstract Tight junctions (TJs) between adjacent Sertoli cells are believed to form immunological barriers that protect spermatogenic cells expressing autoantigens from autoimmune responses. However, there is no direct evidence that Sertoli cell TJs (SCTJs) do indeed form immunological barriers. Here, we analyzed male mice lacking claudin-11 (Cldn11), which encodes a SCTJ component, and found autoantibodies against antigens of spermatocytes/spermatids in their sera. Defective spermatogenesis in Cldn11-deficient mice was not restored on a recombination activating gene 2 (Rag2) knockout background lacking mature T and B lymphocytes. This suggests that adaptive immune responses to spermatogenic cells are not a cause of defective spermatogenesis in Cldn11-deficient mice. Further analyses showed that Cldn11 knockout impaired Sertoli cell polarization, localization of stem cell factor (SCF) (a key molecule for maintaining differentiating spermatogonia) to the basal compartment of seminiferous tubules, and also proliferation of differentiating spermatogonia. We propose that CLDN11 creates a microenvironment for SCF-mediated spermatogonial proliferation at the basal compartment via Sertoli cell polarization.https://doi.org/10.1038/s42003-025-07592-0 |
| spellingShingle | Taichi Sugawara Kayoko Sonoda Nattapran Chompusri Kazuhiro Noguchi Seiji Okada Mikio Furuse Tomohiko Wakayama Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor Communications Biology |
| title | Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor |
| title_full | Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor |
| title_fullStr | Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor |
| title_full_unstemmed | Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor |
| title_short | Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor |
| title_sort | claudin 11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor |
| url | https://doi.org/10.1038/s42003-025-07592-0 |
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