Pediatric IBD patients show medication and disease activity dependent changes in NK cell and CD4 memory T cell populations.

Objectives: CD4+ memory T cells facilitate long-termed adaptive immune responses while NK cells are predominately rapid effector cells with significant functions for both intestinal homeostasis and inflammation. We wanted to study both populations in health and pediatric inflammatory bowel disease (IBD) and correlate them with disease activity and medication. Methods: We performed flow cytometric analyses of peripheral blood CD4 + CD45RO+ memory T cells and CD3-CD16 + CD56+ NK cells in 30 patients with IBD and 31 age-matched controls and correlated percentages of subsets with disease activity (PUCAI/PCDAI) and medication. Results: We found a significant reduction of peripheral NK cells in overall IBD patients with both clinical remission and disease activity, which was even more pronounced in patients treated with azathioprine. Otherwise, circulating CD4+ memory T cell populations were significantly enhanced in active IBD compared to controls. Enhancement of memory T cells was particularly found in new onset disease and correlated with disease activity scores. Discussion: Our single center cohort confirms previous results showing enhanced memory T cell populations in pediatric IBD patients, which correlate with disease activity scores. CD4+ memory T cells are a relevant pathogenic leukocyte population for disease development and perpetuation in IBD. In addition, we found a decrease of NK cells in IBD patients, which was pronounced by use of azathioprine. Surveillance of both cellular populations could possibly serve as biomarker for therapy control in pediatric IBD.

Change of Sleep Stage during Gastroesophageal Reflux in Infants.

INTRODUCTION: This study intended to explore the existence of a temporal association of changes of sleep stage and gastroesophageal reflux (GER) in infants. MATERIALS AND METHODS: Documentation of sleep stage and GER was conducted via the use of synchronized polygraphic recording combined with impedance-pH-metry in 15 infants. The total recording-time (Rt) was divided into GER-"window-time" (five seconds before and after the onset of a GER episode), "remaining GER time", and "GER-free time", and analyzed for changes of sleep stage. RESULTS: a total of 462 GER episodes were identified during Rt (151.1 h) in all infants. During 1.3 h of window-time; 61 changes of sleep stage (47/h); during 5.9 h of Remaining GER-time, 139 changes of sleep stage (24/h); and during 143.9 h of GER-free time, 4087 changes of sleep stage (28/h) were documented. Change of sleep stage was strongly associated with the onset of GER (p < 0.02 and p < 0.05, respectively). CONCLUSIONS: There is a strong temporal association between sleep irregularities, i.e., changes of sleep and episodes of GER in infants. When dealing with disturbed sleep in infants, GER should be considered by caregivers.

Cognate recognition of microbial antigens defines constricted CD4+ T cell receptor repertoires in the inflamed colon.

Key aspects of intestinal T cells, including their antigen specificity and their selection by the microbiota and other intestinal antigens, as well as the contribution of individual T cell clones to regulatory and effector functions, remain unresolved. Here we tracked adoptively transferred T cell populations to specify the interrelation of T cell receptor repertoire and the gut antigenic environment. We show that dominant TCRα clonotypes were shared between interferon-γ- and interleukin-17-producing but not regulatory Foxp3+ T cells. Identical TCRα clonotypes accumulated in the colon of different individuals, whereas antibiotics or defined colonization correlated with the expansion of distinct expanded T cell clonotypes. Our results demonstrate key aspects of intestinal CD4+ T cell activation and suggest that few microbial species exert a dominant effect on the intestinal T cell repertoire during colitis. We speculate that dominant proinflammatory T cell clones might provide a therapeutic target in human inflammatory bowel disease.

Upregulation of Anti-Oxidative Stress Response Improves Metabolic Changes in L-Selectin-Deficient Mice but Does Not Prevent NAFLD Progression or Fecal Microbiota Shifts.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem. NAFLD progression involves a complex interplay of imbalanced inflammatory cell populations and inflammatory signals such as reactive oxygen species and cytokines. These signals can derive from the liver itself but also from adipose tissue or be mediated via changes in the gut microbiome. We analyzed the effects of a simultaneous migration blockade caused by L-selectin-deficiency and an enhancement of the anti-oxidative stress response triggered by hepatocytic Kelch-like ECH-associated protein 1 (Keap1) deletion on NAFLD progression. (2) Methods: L-selectin-deficient mice (Lsel-/-Keap1flx/flx) and littermates with selective hepatic Keap1 deletion (Lsel-/-Keap1Δhepa) were compared in a 24-week Western-style diet (WD) model. (3) Results: Lsel-/-Keap1Δhepa mice exhibited increased expression of erythroid 2-related factor 2 (Nrf2) target genes in the liver, decreased body weight, reduced epidydimal white adipose tissue with decreased immune cell frequencies, and improved glucose response when compared to their Lsel-/-Keap1flx/flx littermates. Although WD feeding caused drastic changes in fecal microbiota profiles with decreased microbial diversity, no genotype-dependent shifts were observed. (4) Conclusions: Upregulation of the anti-oxidative stress response improves metabolic changes in L-selectin-deficient mice but does not prevent NAFLD progression and shifts in the gut microbiota.