CD4+ and CD8+ T cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis

Jacobo, Patricia Verónica; Pérez, Cecilia Valeria; Theas, María Susana; Guazzone, Vanesa Anabella; Lustig, Livia

doi:10.1530/rep-10-0362

Cited by 60 publications

(41 citation statements)

References 53 publications

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“…Similar to the CD4 + T cell population, CD8 + effector T cells can be defined on the basis of pro- and anti-inflammatory cytokine responses after ex vivo restimulation [54]. The frequency of cytokine producing CD8 + T cells was determined based on appropriate isotype controls (Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

L. plantarum, L. salivarius, and L. lactis Attenuate Th2 Responses and Increase Treg Frequencies in Healthy Mice in a Strain Dependent Manner

et al. 2012

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Many studies on probiotics are aimed at restoring immune homeostasis in patients to prevent disease recurrence or reduce immune-mediated pathology. Of equal interest is the use of probiotics in sub-clinical situations, which are characterized by reduced immune function or low-grade inflammation, with an increased risk of infection or disease as a consequence. Most mechanistic studies focus on the use of probiotics in experimental disease models, which may not be informative for these sub-clinical conditions. To gain better understanding of the effects in the healthy situation, we investigated the immunomodulatory effects of two Lactobacillus probiotic strains, i.e. L. plantarum WCFS1 and L. salivarius UCC118, and a non-probiotic lactococcus strain, i.e. L. lactis MG1363, in healthy mice. We studied the effect of these bacteria on the systemic adaptive immune system after 5 days of administration. Only L. plantarum induced an increase in regulatory CD103+ DC and regulatory T cell frequencies in the spleen. However, all three bacterial strains, including L. lactis, reduced specific splenic T helper cell cytokine responses after ex vivo restimulation. The effect on IFN-γ, IL5, IL10, and IL17 production by CD4+ and CD8+ T cells was dependent on the strain administered. A shared observation was that all three bacterial strains reduced T helper 2 cell frequencies. We demonstrate that systemic immunomodulation is not only observed after treatment with probiotic organisms, but also after treatment with non-probiotic bacteria. Our data demonstrate that in healthy mice, lactobacilli can balance T cell immunity in favor of a more regulatory status, via both regulatory T cell dependent and independent mechanisms in a strain dependent manner.

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Section: Resultsmentioning

confidence: 99%

L. plantarum, L. salivarius, and L. lactis Attenuate Th2 Responses and Increase Treg Frequencies in Healthy Mice in a Strain Dependent Manner

et al. 2012

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Section: Discussionmentioning

confidence: 99%

“…The cytokine interleukin-17, ukin-17 (IL-17 or IL-17A) and the pathology associated with aberrant IL-17 signaling played an important role in maintaining the testicular immune including cell immunity, mucosal immunity and cytokines, especially in experimental autoimmune orchitis (EAO)184849. Jacobo P. et al 49. reported that in EAO testis developed by active immunization with spermatic antigens, testis-infiltrating cells revealed an increased number of macrophages, dendritic cells and T cell subsets including Th17 cells so that TNF-α, IL-17 and other immune cells secreted pro-inflammatory cytokines, which disrupted the normal testicular immune suppressor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Role of IL-17 Pathways in Immune Privilege: A RNA Deep Sequencing Analysis of the Mice Testis Exposure to Fluoride

Huo

Han

Sun

et al. 2016

Sci Rep

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We sequenced RNA transcripts from the testicles of healthy male mice, divided into a control group with distilled water and two experimental groups with 50 and 100 mg/l NaF in drinking water for 56 days. Bowtie/Tophat were used to align 50-bp paired-end reads into transcripts, Cufflinks to measure the relative abundance of each transcript and IPA to analyze RNA-Sequencing data. In the 100 mg/l NaF-treated group, four pathways related to IL-17, TGF-β and other cellular growth factor pathways were overexpressed. The mRNA expression of IL-17RA, IL-17RC, MAP2K1, MAP2K2, MAP2K3 and MAPKAPK2, monitored by qRT-PCR, increased remarkably in the 100 mg/L NaF group and coincided with the result of RNA-Sequencing. Fluoride exposure could disrupt spermatogenesis and testicles in male mice by influencing many signaling pathways and genes, which work on the immune signal transduction and cellular metabolism. The high expression of the IL-17 signal pathway was a response to the invasion of the testicular immune system due to extracellular fluoride. The PI3-kinase/AKT, MAPKs and the cytokines in TGF-β family were contributed to control the IL-17 pathway activation and maintain the immune privilege and spermatogenesis. All the findings provided new ideas for further molecular researches of fluorosis on the reproduction and immune response mechanism.

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“…Ten-week-old male mice were used for EAO induction based on a previously described protocol [25]. In brief, male germ cells from 10-week-old mice were homogenized in 1× PBS.…”

Section: Eao Inductionmentioning

confidence: 99%

Roles of Toll-Like Receptors 2 and 4 in Mediating Experimental Autoimmune Orchitis Induction in Mice1

Liu

Zhao

Chen

et al. 2015

Biology of Reproduction

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The mammalian testis is an immunoprivileged site where male germ cell antigens are immunologically tolerated under physiological conditions. However, some pathological conditions can disrupt the immunoprivileged status and induce autoimmune orchitis, an etiological factor of male infertility. Mechanisms underlying autoimmune orchitis induction are largely unknown. The present study investigated the roles of Toll-like receptor 2 (TLR2) and TLR4 in mediating the induction of experimental autoimmune orchitis (EAO) in mice after immunization with male germ cell antigens emulsified with complete Freund adjuvant. Wild-type (WT) mice developed severe EAO after three immunizations, which was characterized by leukocyte infiltration, autoantibody production, and impaired spermatogenesis. Tlr2 or Tlr4 deficient mice showed relatively low susceptibility to EAO induction compared with WT mice. Notably, Tlr2 and Tlr4 double knockout mice were almost completely protected from EAO induction. Moreover, we demonstrated that TLR2 was crucial in mediating autoantibody production in response to immunization. The results imply that TLR2 and TLR4 cooperatively mediate EAO induction.

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CD4+ and CD8+ T cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis

Cited by 60 publications

References 53 publications

L. plantarum, L. salivarius, and L. lactis Attenuate Th2 Responses and Increase Treg Frequencies in Healthy Mice in a Strain Dependent Manner

L. plantarum, L. salivarius, and L. lactis Attenuate Th2 Responses and Increase Treg Frequencies in Healthy Mice in a Strain Dependent Manner

Role of IL-17 Pathways in Immune Privilege: A RNA Deep Sequencing Analysis of the Mice Testis Exposure to Fluoride

Roles of Toll-Like Receptors 2 and 4 in Mediating Experimental Autoimmune Orchitis Induction in Mice1

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