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Loss of Zbtb32 in NOD mice does not significantly alter T cell responses.

ABSTRACT: Background : We previously identified the transcriptional regulator Zbtb32 as a factor that can promote T cell tolerance in the Non-Obese Diabetic (NOD) mouse, a model of Type 1 diabetes. Antigen targeted to DCIR2 ⁺ dendritic cells (DCs) in vivo inhibited both diabetes and effector T cell expansion in NOD mice. Furthermore, Zbtb32 was preferentially induced in autoreactive CD4 T cells stimulated by these tolerogenic DCIR2 ⁺ DCs, and overexpression of Zbtb32 in islet-specific T cells inhibited the diabetes development by limiting T cell proliferation and cytokine production. Methods : To further understand the role of Zbtb32 in T cell tolerance induction, we have now used CRISPR to target the Zbtb32 gene for deletion directly in NOD mice and characterized the mutant mice. We hypothesized that the systemic loss of Zbtb32 in NOD mice would lead to increased T cell activation and increased diabetes pathogenesis. Results : Although NOD.Zbtb32 ^-/- male NOD mice showed a trend towards increased diabetes incidence compared to littermate controls, the difference was not significant. Furthermore, no significant alteration in lymphocyte number or function was observed. Importantly, in vitro stimulation of lymphocytes from NOD.Zbtb32 ^-/- mice did not produce the expected hypersensitive phenotype observed in other genetic strains, potentially due to compensation by homologous genes. Conclusions : The loss of Zbtb32 in the NOD background does not result in the expected T cell activation phenotype.

SUBMITTER: Coley WD

PROVIDER: S-EPMC5909056 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFlow-mediated dilation (FMD) and carotid intima-medial thickness (CIMT), measured by ultrasound, are widely used to test the efficacy of cardioprotective interventions. Although assessment methods vary, automated edge-detecting image analysis software is routinely used to measure changes in FMD and CIMT. We aimed to quantify the effect that commonly adjusted ultrasound settings have on arterial lumen and wall thickness measurements made with CIMT measurement software.MethodsWe constructed phantom arteries from a tissue-mimicking agar compound and scanned them in a water bath with a 10 MHz multi-frequency linear-array probe attached to a high-resolution ultrasound machine. B-mode images of the phantoms were recorded with dynamic range (DR) and gain set at five decibel (dB) increments from 40 dB to 60 dB and -10 dB to +10 dB respectively. Lumen diameter and wall-thickness were measured off-line using CIMT measurement software.ResultsLumen measurements: there was a strong linear relationship between DR and gain and measured lumen diameter. For a given gain level, a 5 dB increase in DR reduced the measured lumen diameter by 0.02 +/- 0.004 mm (p < 0.001). For a given DR level, a 5 dB increase in gain reduced measured lumen diameter by 0.04 +/- 0.004 mm (p < 0.001). A 5 mm increase in distance between the ultrasound probe and the artery reduced measured lumen diameter by 0.04 +/- 0.03 mm (p < 0.001)CIMT measurements: For a fixed gain level, a 5 dB increase in DR increased measured wall thickness by 0.003 +/- 0.002 mm (p < 0.001). The effects of increasing gain were not consistent and appeared to vary depending on the distance between the artery and the ultrasound probe and the thickness of the artery wall.ConclusionDR, gain and probe distance significantly alter lumen diameter and CIMT measurements made using image analysis software. When CIMT and FMD are used to test the efficacy of cardioprotective interventions, the DR, gain and probe position used to record baseline scans should be documented and replicated in post-treatment scans in individual trial subjects. If more than one sonographer or imaging centre is used to collect data, the study protocol should document specific DR and gain settings to be used in all subjects.

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Loss of Zbtb32 in NOD mice does not significantly alter T cell responses.

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