CTLA-4-expressing ILC3s restrain interleukin-23-mediated inflammation.

Interleukin (IL-)23 is a major mediator and therapeutic target in chronic inflammatory diseases that also elicits tissue protection in the intestine at homeostasis or following acute infection. However, the mechanisms that shape these beneficial versus pathological outcomes remain poorly understood. To address this gap in knowledge, we performed single-cell RNA sequencing on all IL-23 receptor-expressing cells in the intestine and their acute response to IL-23, revealing a dominance of T cells and group 3 innate lymphoid cells (ILC3s).

ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut.

Microbial colonization of the mammalian intestine elicits inflammatory or tolerogenic T cell responses, but the mechanisms controlling these distinct outcomes remain poorly understood, and accumulating evidence indicates that aberrant immunity to intestinal microbiota is causally associated with infectious, inflammatory and malignant diseases. Here we define a critical pathway controlling the fate of inflammatory versus tolerogenic T cells that respond to the microbiota and express the transcription factor RORγt. We profiled all RORγt immune cells at single-cell resolution from the intestine-draining lymph nodes of mice and reveal a dominant presence of T regulatory (T) cells and lymphoid tissue inducer-like group 3 innate lymphoid cells (ILC3s), which co-localize at interfollicular regions.

ZBTB46 defines and regulates ILC3s that protect the intestine.

RORγt is a lineage-specifying transcription factor that is expressed by immune cells that are enriched in the gastrointestinal tract and promote immunity, inflammation and tissue homeostasis. However, fundamental questions remain with regard to the cellular heterogeneity among these cell types, the mechanisms that control protective versus inflammatory properties and their functional redundancy. Here we define all RORγt immune cells in the intestine at single-cell resolution and identify a subset of group 3 innate lymphoid cells (ILC3s) that expresses ZBTB46, a transcription factor specifying conventional dendritic cells.

Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.

Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the importance and regulation of these changes remain unclear. We found that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels.

Pulmonary Manifestations in Adolescents With Inflammatory Bowel Disease.

. The available literature on pulmonary disease in pediatric inflammatory bowel disease is limited. We evaluated the prevalence of pulmonary manifestations in pediatric inflammatory bowel disease and their association with disease severity.

Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2.

Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract. The protective effects of IL-2 involve the generation, maintenance and function of regulatory T (T) cells, and the use of low doses of IL-2 has emerged as a potential therapeutic strategy for patients with inflammatory bowel disease. However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined.

Assuring Quality for Non-hospital-based Biologic Infusions in Pediatric Inflammatory Bowel Disease: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

The primary aim of this Clinical Report by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition is to provide formal guidance to pediatric gastroenterologists and clinicians, health systems, and insurance payers regarding home- and office-based infusions for biologic therapies in pediatric inflammatory bowel disease. Patients in North America are increasingly denied coverage by payers based on "place of service" codes at hospital-based infusion units where the treating clinicians primarily provide care. A task force with topic expertise generated 8 best practice recommendations to ensure quality of care for pediatric patients with inflammatory bowel disease receiving non-hospital-based biologic infusions.

Pediatric Gastroenterologists' Approach to Venous Thromboembolism Prophylaxis in Pediatric Inflammatory Bowel Disease.

The risk of venous thromboembolism (VTE) is significantly increased in patients with inflammatory bowel disease (IBD). For the adult population, prophylaxis guidelines exist to help guide physicians in their management of high-risk IBD patients. Although it is known that children with IBD also experience increased rates of VTE, there is no clear consensus on how best to prevent these unwanted complications.

Health Care Maintenance for the Pediatric Patient With Inflammatory Bowel Disease.

Nearly one-quarter of patients with inflammatory bowel disease (IBD) are younger than 20 years of age at diagnosis. Furthermore, the incidence of IBD in children continues to increase. Nevertheless, variation in management exists within the care of patients with IBD with regards to disease screening and preventive care.

Cerebral venous thrombosis in inflammatory bowel disease.

Cerebral venous thrombosis (CVT) is a rare but devastating complication of inflammatory bowel disease (IBD). Here we describe six IBD patients with cerebral venous thrombosis. The patients presented with hours to days of headache and were found to have venous thrombosis on imaging.

Development and validation of a celiac disease quality of life instrument for North American children.

Objective: Given the social constraints imposed by a gluten-free diet, it can be hypothesized that children with celiac disease (CD) living in the United States have a reduced health-related quality of life (HRQOL); however, there is no validated CD-specific HRQOL instrument for children living in the United States. The goals of this study were to develop and validate a CD-specific HRQOL instrument for children 8 to 18 years of age with CD and to report HRQOL in these children using both generic- and disease-specific instruments.

Methods: This was a prospective study using focus group methodology to develop a CD-specific HRQOL instrument that was then administered to children 8 to 18 years of age with CD living throughout the United States.

Magnetic resonance enterography and wireless capsule endoscopy in the evaluation of patients with inflammatory bowel disease.

Background: Magnetic resonance enterography (MRE) is increasingly used in children due to growing concerns of radiation.

Objective: To determine the performance of MRE, imaging findings were compared to wireless capsule endoscopy (WCE) and histology results in children with/or suspected inflammatory bowel disease (IBD).

Materials And Methods: Pathology and WCE reports were retrospectively reviewed in 23 patients who had MRE.