Lymph node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin 17 (IL-17)-producing T helper (TH17) cells promote inflammation through induction of cytokines and chemokines in peripheral tissues. We demonstrate a critical requirement for IL-17 in the proliferation of lymph node (LN) and spleen stromal cells, particularly fibroblastic reticular cells (FRCs), during experimental autoimmune encephalomyelitis and colitis. Without IL-17 receptor signaling, activated FRCs underwent cell cycle arrest and ultimately apoptosis, accompanied by signs of nutrient stress in vivo. IL-17 signaling in FRCs was not required for TH17 cell development, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. IL-17 induction of the transcriptional coactivator IκBζ mediated increased glucose uptake and mitochondrial Cpt1a expression. Hence, IL-17 produced by locally differentiating TH17 cells is an important driver of inflamed LN stromal cell activation, through metabolic reprogramming required to support proliferation and survival.
ObjectiveTo assess the effect of storage time and temperature on complete blood count (CBC) and comprehensive metabolic panel (CMP) testing.MethodsPubMed, EMBASE, the Cochrane Library of Systematic Reviews, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), WanFang databases and SinoMed databases were searched up to May 2017. Clinical trials with adult whole blood samples were identified. Paired reviewers independently screened, extracted data and evaluated the quality of evidence (MINORS tool). Analyses were conducted using Revman 5.3 and Stata 14.0.ResultsA total of 89 studies were confirmed. For CBC, except MPV, most parameters were stable at least for 24 h. Some indices, such as WBC, PLt, HCT, HGB and MCH were stable up to 3 d. However, stable CMP test results could only be acquired within 12 h. at 4 °C, including GLU, AST, ALT, Na, ALB, Cl, DBIL, TC, TG and ALP. Values were less stable when stored at RT.ConclusionsSpecimens stored > 12 h. for CMP may generate unreliable results. For CBC, samples could reliably be stored for 24 h. For longer storage, refrigeration (at 4 °C) would be a better choice.
AIMTo assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC).METHODSFrom March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach’s α coefficient, the Spearman correlation test and Wilcoxon rank sum test.RESULTSThe EORTC QLQ-CR29 showed satisfactory reliability (α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (α = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS ≤ 80; KPS > 80). Body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients.CONCLUSIONThe EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.
The STAT3 signaling pathway is required for early Th17 cell development, and therapies targeting this pathway are used for autoimmune disease. However, the role of STAT3 in maintaining inflammatory effector Th17 cell function has been unexplored. Th17ΔSTAT3 mice, which delete STAT3 in effector Th17 cells, were resistant to experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Th17 cell numbers declined after STAT3 deletion, corresponding to reduced cell cycle. Th17ΔSTAT3 cells had increased IL-6–mediated phosphorylation of STAT1, known to have antiproliferative functions. Th17ΔSTAT3 cells also had reduced mitochondrial membrane potential, which can regulate intracellular Ca2+. Accordingly, Th17ΔSTAT3 cells had reduced production of proinflammatory cytokines when stimulated with myelin antigen but normal production of cytokines when TCR-induced Ca2+ flux was bypassed with ionomycin. Thus, early transcriptional roles of STAT3 in developing Th17 cells are later complimented by noncanonical STAT3 functions that sustain pathogenic Th17 cell proliferation and cytokine production.
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