CCR6 promotes steady-state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance.

The intestinal lamina propria (LP) contains antigen-presenting cells with features of dendritic cells and macrophages, collectively referred to as mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is thought to play an important role in multiple facets of intestinal immunity including imprinting MNPs with the ability to induce IgA production, inducing the expression of gut homing molecules on T cells, facilitating the capture of luminal antigens and microbes, and subsequent immune responses in the mesenteric lymph node (MLN). However, the factors promoting this process in the steady state are largely unknown, and in vivo models to test and confirm the importance of LP-MNP association with the epithelium for these outcomes are unexplored. Evaluation of epithelial expression of chemoattractants in mice where MNP-epithelial associations were impaired suggested CCL20 as a candidate promoting epithelial association. Expression of CCR6, the only known receptor for CCL20, was required for MNPs to associate with the epithelium. LP-MNPs from CCR6-/- mice did not display defects in acquiring antigen and stimulating T-cell responses in ex vivo assays or in responses to antigen administered systemically. However, LP-MNPs from CCR6-deficient mice were impaired at acquiring luminal and epithelial antigens, inducing IgA production in B cells, inducing immune responses in the MLN, and capturing and trafficking luminal commensal bacteria to the MLN. These findings identify a crucial role for CCR6 in promoting LP-MNPs to associate with the intestinal epithelium in the steady state to perform multiple functions promoting gut immune homeostasis.

Surgery for chronic idiopathic constipation: pediatric and adult patients - a systematic review.

BACKGROUND: Chronic idiopathic constipation (CIC) is a substantial problem in pediatric and adult patients with similar symptoms and workup; however, surgical management of these populations differs. We systematically reviewed the trends and outcomes in the surgical management of CIC in pediatric and adult populations. METHODS: A literature search was performed using Ovid MEDLINE, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov between January 1, 1995 and June 26, 2020. Clinical trials and retrospective and prospective studies of patients of any age with a diagnosis of CIC with data of at least 1 outcome of interest were selected. The interventions included surgical resection for constipation or antegrade continence enema (ACE) procedures. The outcome measures included bowel movement frequency, abdominal pain, laxative use, satisfaction, complications, and reinterventions. RESULTS: Adult patients were most likely to undergo resection (94%), whereas pediatric patients were more likely to undergo ACE procedures (96%) as their primary surgery. Both ACE procedures and resections were noted to improve symptoms of CIC; however, ACE procedures were associated with higher complication and reintervention rates. CONCLUSION: Surgical management of CIC in pediatric and adult patients differs with pediatric patients receiving ACE procedures and adults undergoing resections. The evaluation of resections and long-term ACE data in pediatric patients should be performed to inform patients and physicians whether an ACE is an appropriate procedure despite high complication and reintervention rates or whether resections should be considered as an initial approach for CIC.

Neonatal cholestasis: opportunities to increase early detection.

OBJECTIVE: To describe primary care management of early and prolonged jaundice in otherwise-healthy term infants to identify opportunities to increase early diagnosis of cholestasis. METHODS: Community-based pediatricians in St Louis, Missouri completed a mailed, anonymous, 29-item survey to assess practice demographics, timing of routine newborn office visits, and the management of early and prolonged neonatal jaundice. RESULTS: A total of 108 of 230 (47%) of eligible physicians responded (mean years in practice, 15.3, SD, 9.4). More respondents were very familiar with national guidelines for management of early (49%) than prolonged (16%) neonatal jaundice. Eighty-six percent reported all newborns were checked with transcutaneous bilirubin before hospital discharge. For transcutaneous bilirubin results at 48 hours of 7, 10, 12 and 15 mg/dL, 1%, 26%, 70%, and 74% of respondents, respectively, would order a fractionated bilirubin. Although the first routine visit usually occurred in the first week after discharge, 25% of physicians reported the 2nd visit was routinely scheduled after 4 weeks of age. Ninety-four percent reported they would obtain a fractionated bilirubin for infants jaundiced beyond 4 weeks of age. If cholestasis was identified at 6 weeks of age, 32% would obtain additional testing without referral to a subspecialist. CONCLUSIONS: Management of early and prolonged neonatal jaundice is variable. Current practices appear to miss opportunities for early diagnosis of cholestasis and referral that are unlikely to be addressed without redesigning systems of care.