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IL17A impairs blood–testis barrier integrity and induces testicular inflammation

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Abstract

Experimental autoimmune orchitis is a useful model for studying testicular inflammation and germ/immune cell interactions. Th17 cells and their hallmark cytokine IL17A were reported to be involved in the development of autoimmune orchitis. The aim of the present work is to investigate the pathogenic role of IL17A in rat testis. In vitro experiments were performed in order to analyze effects of IL17A on Sertoli cell tight junctions. The addition of IL17A to normal rat Sertoli cell cultures induced a significant decline in transepithelial electrical resistance and a reduction of occludin expression and redistribution of occludin and claudin 11, altering the Sertoli cell tight junction barrier. Intratesticular injection of 1 μg of recombinant rat IL17A to Sprague–Dawley rats induced increased blood–testis barrier permeability, as shown by the presence of biotin tracer in the seminiferous tubule adluminal compartment, and delocalization of occludin and claudin 11. Results showed that IL17A induced focal inflammatory cell infiltration in the interstitium and germ cell sloughing in adjacent seminiferous tubules. Moreover, an increase in TUNEL+ apoptotic germ cells was also observed. Inflammatory ED1+ macrophages were the main population infiltrating the interstitium following IL17A injection. This correlated with an increase in mRNA expression of the monocyte chemoattractant protein Ccl2, its receptor Ccr2 and the vascular cell adhesion molecule Vcam1. Overall results suggest a relevant role of IL17A in the development of testicular inflammation, facilitating the recruitment of immune cells to the testicular interstitium and inducing impairment of blood–testis barrier function.

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Acknowledgments

This work was supported by the Universidad de Buenos Aires (grant number 20020100100447) and the Consejo Nacional de Investigaciones Científicas y Técnicas (grant numbers 11220110100930, 11220080100806). We are grateful to Shuichi Hirai for his suggestions and excellent assistance in PCR experiments. We thank Cecilia García for her technical assistance in histological procedures and the Instituto Nacional de Microbiología “A. Malbrán”, División Vacunas Bacterianas, for their generous donation of Bordetella pertussis.

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Authors and Affiliations

  1. Instituto de Investigaciones Biomédicas UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Cecilia Valeria Pérez, Munekazu Naito, Livia Lustig & Patricia Verónica Jacobo

  2. Centro de Investigaciones Endocrinológicas CONICET, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

    Eliana Herminia Pellizzari, Selva Beatriz Cigorraga & María Noel Galardo

  3. Department of Anatomy, Tokyo Medical University, Tokyo, Japan

    Munekazu Naito

  4. Paraguay 2155, piso 10, C1121ABG, Ciudad Autónoma de Buenos Aires, Argentina

    Cecilia Valeria Pérez

Authors
  1. Cecilia Valeria Pérez
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  2. Eliana Herminia Pellizzari
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  3. Selva Beatriz Cigorraga
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  4. María Noel Galardo
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  5. Munekazu Naito
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  6. Livia Lustig
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  7. Patricia Verónica Jacobo
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Correspondence to Cecilia Valeria Pérez.

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Pérez, C.V., Pellizzari, E.H., Cigorraga, S.B. et al. IL17A impairs blood–testis barrier integrity and induces testicular inflammation. Cell Tissue Res 358, 885–898 (2014). https://doi.org/10.1007/s00441-014-1995-5

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  • DOI: https://doi.org/10.1007/s00441-014-1995-5

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