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Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild-type and pituitary adenylate cyclase-activating polypeptide-deficient mice.
American Journal of Reproductive Immunology ( IF 3.6 ) Pub Date : 2019-12-13 , DOI: 10.1111/aji.13212
Matyas Meggyes 1, 2 , Adrienn Lajko 1 , Balazs Daniel Fulop 3 , Dora Reglodi 3 , Laszlo Szereday 1, 2
Affiliation  

PROBLEM Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP-deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating, and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune-privileged environment in male PACAP-deficient mice. METHOD OF STUDY We performed detailed immunophenotyping of testicular immune cells and investigated the expression of TIM-3 and PD-1 Immune checkpoint molecules of immune cells together with the detection of galectin-9 and perforin. We investigated the percentage of numerous immune cell populations in the testis of wild-type and PACAP-deficient mice. RESULTS We demonstrated a significant increase in the frequency of testicular CD8+ T cells together with the decrease in Treg cell number obtained from PACAP KO mice compared with wild-type mice. Investigating Immune checkpoint receptors, only PD-1 showed a significantly decreased expression in CD8+ T cells in PACAP KO mice compared with wild-type suggesting an impaired PD-1/PD-L1 pathway. Regarding TIM-3 expression, we did not find any significant difference between the investigated groups. CONCLUSION We hypothesize that these local changes may result in an immune activation with disturbed testicular immunoregulation in PACAP KO mice; however, determining the exact function requires further investigations. Our data further support the view that besides a systemic immune tolerance, localized active immunosuppression is involved in the regulation of testicular immune privilege.

中文翻译:

在野生型和垂体腺苷酸环化酶激活多肽缺陷型小鼠中表达免疫检查点分子的睾丸免疫细胞的表型表征。

问题垂体腺苷酸环化酶激活多肽(PACAP)是一种神经肽,在神经系统和周围器官(包括生殖系统的器官)中具有多种调节功能。缺乏PACAP的雄性小鼠具有几种形态,生化,行为缺陷,并且在精子发生过程中显示出受干扰的信号,从而影响了PACAP KO小鼠的生育能力。生殖功能,如生育能力,交配和母性行为已被广泛研究,但是对于雄性PACAP缺陷小鼠的睾丸免疫特权环境,没有免疫分析可用。研究方法我们对睾丸免疫细胞进行了详细的免疫表型分析,研究了免疫细胞TIM-3和PD-1免疫检查点分子的表达以及半乳凝素9和穿孔素的检测。我们调查了野生型和PACAP缺陷型小鼠睾丸中大量免疫细胞群体的百分比。结果我们证明,与野生型小鼠相比,PACAP KO小鼠的睾丸CD8 + T细胞频率显着增加,而Treg细胞数量减少。研究免疫检查点受体,与野生型相比,PACAP KO小鼠中只有PD-1在CD8 + T细胞中的表达显着降低,表明PD-1 / PD-L1途径受损。关于TIM-3表达,我们在研究组之间没有发现任何显着差异。结论我们推测,这些局部变化可能导致PACAP KO小鼠的免疫活化以及睾丸免疫调节受到干扰。但是,确定确切功能需要进一步调查。
更新日期:2019-11-01
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