The physiological stresses that diminish tissue stem-cell characteristics remain largely unknown. We previously reported that type I interferon (IFN), which is essential for host antiviral responses, is a physiological stressor for hematopoietic stem cells (HSCs) and small intestinal stem cells (ISCs) and that interferon regulatory factor-2 (IRF2), which attenuates IFN signaling, maintains their stemness. Here, using a dextran sodium sulfate (DSS)-induced colitis model, we explore the role of IRF2 in maintaining colonic epithelial stem cells (CoSCs). In mice with a conditional Irf2 deletion in the intestinal epithelium (hereafter Irf2ΔIEC mice), both the number and the organoid-forming potential of CoSCs were markedly reduced. Consistent with this finding, the ability of Irf2ΔIEC mice to regenerate colon epithelium after inducing colitis was severely impaired, independently of microbial dysbiosis. Mechanistically, CoSCs differentiated prematurely into transit-amplifying (TA) cells in Irf2ΔIEC mice, which might explain their low CoSC counts. A similar phenotype was induced in wild-type mice by repeated injections of low doses of poly(I:C), which induces type I IFN. Collectively, we demonstrated that chronic IFN signaling physiologically stresses CoSCs. This study provides new insight into the development of colitis and molecular mechanisms that maintain functional CoSCs throughout life.

Purpose: To evaluate the repeatability and reproducibility of the measurement of retinal arteriole pulse waveforms using a novel fully-automated Doppler optical coherence tomography (DOCT) flowmeter in healthy subjects.Methods: Twenty eyes of 20 healthy subjects were included to test the intrasession repeatability of pulse waveform analysis. DOCT measurements were performed based on a newly developed instantaneous Doppler angle measurement method. Upstroke time (UT), which is the time from the minimum to the maximum retinal blood velocity, and the resistance index (RI) of the retinal arteriole pulse waveform were measured. Coefficients of variation (CVs) and intraclass correlation coefficients (ICCs) were calculated. Interdevice reproducibility between two instruments was assessed in five eyes of five subjects.Results: The mean UT was 130.3 ms (range, 110.1-152.1 ms), and the mean RI was 0.66 (range, 0.51-0.82). The respective ICCs of UT and the RI for the intrasession repeatability of assessment were 0.87 and 0.78. The respective CVs of UT and the RI were 6.6 6 3.3% and 4.7 6 2.1%. Regarding interdevice reproducibility, there were no significant differences between the measurements derived from the instruments (P . 0.05). Conclusions:Pulse waveform measurement in retinal arterioles using a fullyautomated DOCT flowmeter exhibited good repeatability and interdevice reproducibility.Translational Relevance: The above-described improved DOCT flowmeter system provides reasonably repeatable measurements of retinal arteriole pulse waveforms, potentially facilitating systemic-circulation abnormality monitoring. The examination of the circulation with the novel device can be potentially useful for evaluating systemic circulation.

Scratching and skin barrier dysfunctions are pivotal features and therapeutic targets of atopic dermatitis (AD); however, time-of-day-dependent variations of these characteristics remain unclear. NC/Tnd mice have been shown to exhibit severe scratching behavior and skin barrier disruption together with the development of spontaneous atopic dermatitis when they are raised under air-uncontrolled environment. In the present study, time-of-day-dependent variations of scratching behavior and transepidermal water loss (TEWL) were evaluated in NC/Tnd mice that developed moderate to severe AD. Analysis of the mice for 24 hr revealed that scratching frequency and duration were increased from in the afternoon to the nocturnal period when locomotor activity was low, and scratching behavior was decreased in the morning. The highest scratching frequency and duration were 3.8- and 4.1-fold increases in the lowest scratching frequency and duration, respectively. In addition, TEWL on the dorsal skin lesion was decreased in the diurnal period, while that was increased in the nocturnal period. The highest TEWL was a 1.3-fold increase in the lowest TEWL. Significant daily variations were detected in scratching frequency and duration and TEWL. These results indicate that NC/Tnd mice are an appropriate mouse model to investigate time-of-day-dependent variations of scratching behavior and skin barrier dysfunctions associated with AD.

Purpose The purpose of this study was to evaluate the diagnostic performance of retinal blood flow (RBF) measured with the Doppler optical coherence tomography (OCT) segmental scanning method to distinguish between healthy and glaucoma eyes. Methods Fifty-eight patients with normal tension glaucoma (NTG) who had a single-hemifield visual field defect and 44 age-matched healthy subjects were enrolled. Retinal nerve fiber layer thickness (RNFLT) was measured with swept-source OCT. Superior and inferior temporal arteries (TAs) and temporal veins (TVs) RBF were measured with Doppler OCT. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to compare the diagnostic performances in the damaged and normal hemispheres. Results Multivariate regression analysis showed TA RBF and TV RBF were significantly reduced in the damaged and normal hemispheres. The ROC analysis showed that the AUC for quadrant RNFLT, TA RBF, and TV RBF were 0.973, 0.909, and 0.872 in the damaged hemisphere, respectively. The AUC values in the normal hemisphere were 0.783, 0.744, and 0.697, respectively. The combination of quadrant RNFLT and TA/TV RBF had a greater AUC than quadrant RNFLT alone in both damaged (AUC = 0.987) and normal (AUC = 0.825) hemispheres. Conclusions In NTG eyes with single-hemifield damage, the RBF was found to be significantly reduced in the damaged and normal hemispheres independent from structural changes. The combination of RNFLT and RBF could improve diagnostic performances for glaucoma. Translational Relevance Combining morphological and blood flow measurements with Doppler OCT may be useful in glaucoma diagnosis.