Biomedical subjects

Monika Fijak

Publications and source records attributed to Monika Fijak.

3 recordsLinked to original sources

PubMed2006

Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis.

Experimental autoimmune orchitis (EAO) in the rat is the primary chronic animal model for the investigation of one of the main causes of male infertility, viz., testicular inflammation. Dendritic cells (DC) are potent antigen-presenting cells that play a fundamental role in autoimmune disease. We investigated the number of DC in normal testis and examined whether DC infiltrated the testis during the development of EAO. EAO was induced by active immunization with testis homogenate and adjuvants in two strains of rat (Wistar and Sprague Dawley). The presence of DC in testis was determined, 50 and 80 days after the first immunization, by immunohistochemical staining with specific antibodies (OX-62 and CD11c), and then the total number of DC was measured by stereological analysis. Labeled cells were found only in the interstitial compartment and within granulomas of EAO animals. The number of DC in EAO testes increased compared with control rats in both strains, whereas the number of OX-62+ and CD11c+ cells in adjuvant controls remained unchanged compared with untreated rats. Interspecies variations in the quantity of DC were found, with the total number of DC per testis in untreated and adjuvant control Sprague-Dawley rats being about three times higher than that seen in Wistar rats. Moreover, the increase in DC numbers at 80 days was less prominent in EAO testes of Sprague-Dawley rats than in the Wistar strain in which EAO was more severe and showed a higher number of granulomae. Thus, we have identified the DC population in normal and chronically inflamed testis. The increase in DC observed in EAO suggests that, under inflammatory conditions, the modified action(s) of these cells is a factor in the induction of the autoimmune response in testis.

Animals↗

PubMed2006

The testis in immune privilege.

The production, differentiation, and presence of male gametes represent inimitable challenges to the immune system, as they are unique to the body and appear long after the maturation of the immune system and formation of systemic self-tolerance. Known to protect germ cells and foreign tissue grafts from autoimmune attack, the 'immune privilege' of the testis was originally, and somewhat simplistically, attributed to the existence of the blood-testis barrier. Recent research has shown a previously unknown level of complexity with a multitude of factors, both physical and immunological, necessary for the establishment and maintenance of the immunotolerance in the testis. Besides the blood-testis barrier and a diminished capability of the large testicular resident macrophage population to mount an inflammatory response, it is the constitutive expression of anti-inflammatory cytokines in the testis by immune and particularly somatic cells, that represents an essential element for local immunosuppression. The role of androgens in testicular immune regulation has long been underestimated; yet, accumulating evidence now shows that they orchestrate the inhibition of proinflammatory cytokine expression and shift cytokine balance toward a tolerogenic environment. Furthermore, the role of the testicular dendritic cells in suppressing antigen-specific immunity and T-lymphocyte activation is discussed. Finally, the active role mast cells play in the induction and amplification of immune responses, both in infertile humans and in experimental models, highlights the importance of preventing mast cell activation to maintain the immune-privileged status of the testis.

Animals↗

PubMed2005

Identification of immunodominant autoantigens in rat autoimmune orchitis.

Infection and inflammation of the genital tract are amongst the leading causes of male infertility. Experimental autoimmune orchitis (EAO) in the rat serves as a model for the investigation of inflammatory testicular impairment. In this study, experiments were conducted to identify the molecules that are responsible for eliciting the autoimmune attack on the testis. EAO was induced in in-bred Wistar rats by active immunization with testis homogenates (EAO group I). Development of disease was observed using histological techniques and a new non-invasive three-dimensional (3D) imaging technology for in vivo monitoring, termed flat-panel volumetric computed tomography (fpvCT). Examination of control and EAO testes demonstrated the superior image quality of high-resolution fpvCT. A proteomics approach using 2D SDS-PAGE and immunoblotting analysis with EAO sera identified 12 spots. Seven were subsequently identified by mass spectrometry as heat shock proteins 60 (Hsp60) and 70 (Hsp70), disulphide isomerase ER-60, alpha-1-anti-trypsin, heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), sperm outer dense fibre major protein 2 (ODF-2), and phosphoglycerate kinase 1. Hsp70, ODF-2, hnRNP H1, and ER-60 were identified by all EAO sera studied. To test the capacity of the identified proteins to elicit testicular autoimmune disease, recombinant proteins were used either individually or in combination to immunize rats (EAO group II). In all groups, the incidence of EAO was 25%. Inflammatory-type (ED1+) and resident (ED2+) macrophages, lymphocytes (CD45RA+), and dendritic cells (Ox-62+) were strongly increased in EAO group II animals, comparable to the testes of EAO I rats. Pre-immunization with a low dose of recombinant Hsp 70, hnRNP H1 or ODF-2 before induction of EAO with testis homogenate significantly delayed the onset of EAO but could not prevent disease. The identification of testicular autoantigens will allow a better understanding of disease pathogenesis and could provide a basis for the development of novel therapies for inflammation-based male infertility.

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