Expression and Localization of Paneth Cells and Their alpha-Defensins in the Small Intestine of Adult Mouse
FRONTIERS IN IMMUNOLOGY
Authors: Nakamura, Kiminori; Yokoi, Yuki; Fukaya, Rie; Ohira, Shuya; Shinozaki, Ryuga; Nishida, Takuto; Kikuchi, Mani; Ayabe, Tokiyoshi
Abstract
Paneth cells contribute to intestinal innate immunity by sensing bacteria and secreting alpha-defensin. In Institute of Cancer Research (ICR) mice, alpha-defensin termed cryptdin (Crp) in Paneth cells consists of six major isoforms, Crp1 to 6. Despite accumulating evidences that alpha-defensin functions in controlling the intestinal microbiota, topographical localization of Paneth cells in the small intestine in relation to functions of alpha-defensin remains to be determined. In this study, we examined the expression level of messenger RNA (mRNA) encoding six Crp-isoforms and Crp immunoreactivities using singly isolated crypts together with bactericidal activities of Paneth cell secretions from isolated crypts of duodenum, jejunum, and ileum. Here we showed that levels of Crp mRNAs in the single crypt ranged from 5 x 10(3) to 1 x 10(6) copies per 5 ng RNA. For each Crp isoform, the expression level in ileum was 4 to 50 times higher than that in duodenum and jejunum. Furthermore, immunohistochemical analysis of isolated crypts revealed that the average number of Paneth cell per crypt in the small intestine increased from proximal to distal, three to seven-fold, respectively. Both Crp1 and 4 expressed greater in ileal Paneth cells than those in duodenum or jejunum. Bactericidal activities in secretions of ileal Paneth cell exposed to bacteria were significantly higher than those of duodenum or jejunum. In germ-free mice, Crp expression in each site of the small intestine was attenuated and bactericidal activities released by ileal Paneth cells were decreased compared to those in conventional mice. Taken together, Paneth cells and their alpha-defensin in adult mouse appeared to be regulated topographically in innate immunity to control intestinal integrity.
Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up
ARTHRITIS RESEARCH & THERAPY
Authors: Klingberg, Eva; Bjorkman, Sofia; Eliasson, Bjorn; Larsson, Ingrid; Bilberg, Annelie
Abstract
Background: Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index; BMI >= 33 kg/m(2)) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12-16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin. The objectives of this follow-up were to study the effects of the weight loss treatment on disease activity in longer term (12 and 24 months) and to study the effects on cardiovascular risk factors. Methods: The patients were assessed with 66/68 joints count, Leeds enthesitis index (LEI), body surface area, blood pressure, BMI, questionnaires and fasting blood samples at the 12- and 24-month visits. Results: In total, 39 and 35 PsA patients attended the 12- and the 24-month visits, respectively. Median weight loss since baseline was 16.0% (IQR 10.5-22.4) and 7.4% (IQR 5.1-14.0) at the 12- and 24-months follow-up. The 66/68 swollen/tender joints score, LEI, CRP and HAQ score were still significantly reduced at the 12- and 24-month visits compared to baseline. The number of patients with Minimal Disease Activity increased from 28.2% (11/39) at baseline, to 38.5% (15/39;p = 0.008) and 45.7% (16/35;p = 0.016) at the 12- and 24-month visits. The weight loss was also associated with improved levels of serum lipids, glucose and urate and the antihypertensive treatment was reduced or stopped in five patients during the follow-up. Conclusions: Weight loss treatment, with VLED included in the program, was associated with long-term improvement of measures of disease activity, self-reported function and markers of the metabolic syndrome after 24-months follow-up.