Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASCs), a mesenchymal fibroblast-like subset that expresses interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). In vitro, ASCs produced TSLP that supported ILC2 accumulation and activation. ILC2s and IL-13 drove reciprocal ASC expansion and IL-33 expression. During helminth infection, ASC depletion impaired lung ILC2 and Th2 cell accumulation and function, which are in part dependent on ASC-derived IL-33. These data indicate that adventitial niches are conserved sites where ASCs regulate type 2 lymphocyte expansion and function.

Presentation, Management, and Child Protective Service Reporting of Children Who Test Positive for Cannabis in an Emergency Room Setting.

OBJECTIVES: Rates of cannabis ingestion among young children are increasing. Small studies have evaluated symptomatology of these children. The literature lacks research regarding factors influencing medical management. Our goal was to 1) understand circumstances leading to exposure over time and 2) gain insight into factors that may influence emergency room management and Child Protective Services reporting over time. METHODS: Retrospective cross-sectional study on children younger than 10 years with cannabis-positive urine drug screens in the emergency room setting. Single-factor analysis of variance and Fisher exact tests were used to assess for trends. Two-tailed t tests and Fisher exact tests were used to compare management of children presenting to the emergency room with chief complaint (CC) "ingestion" versus those without. RESULTS: Of the 179 children, the mean age was 3.7 years and 48% were boys. We observed a significant increase over time in cannabis-positive children. The most common location of exposure was the primary residence (54%), with parents as the most frequent users (46%). In the emergency department, the most common CC was ingestion followed by altered mental status and fatigue. Children with an "ingestion" CC were managed with less testing than those with other CCs. They received fewer needle sticks (43% vs 91%), less imaging (5% vs 56% computed tomography heads), and fewer procedures (0% vs 8% lumbar punctures). Children with "ingestion" CC were less likely to be reported to Child Protective Services. CONCLUSIONS: Pediatric cannabis exposures are increasing and have a wide array of clinical presentations that complicate emergency room management. Parental report of cannabis ingestion seems to impact and reduce potentially unnecessary testing.

Nur77 Links Chronic Antigen Stimulation to B Cell Tolerance by Restricting the Survival of Self-Reactive B Cells in the Periphery.

Nur77 (Nr4a1) belongs to a small family of orphan nuclear receptors that are rapidly induced by BCR stimulation, yet little is known about its function in B cells. We have previously characterized a reporter of Nr4a1 transcription, Nur77-eGFP, in which GFP expression faithfully detects Ag encounter by B cells in vitro and in vivo. In this study, we report that Nur77 expression correlates with the degree of self-reactivity, counterselection, and anergy among individual B cell clones from two distinct BCR transgenic mouse models but is dispensable for all of these tolerance mechanisms. However, we identify a role for Nur77 in restraining survival of self-reactive B cells in the periphery under conditions of competition for a limited supply of the survival factor BAFF. We find that Nur77 deficiency results in the progressive accumulation of self-reactive B cells in the mature repertoire with age and is sufficient to break B cell tolerance in VH3H9 H chain transgenic mice. We thus propose that Nur77 is upregulated in self-reactive B cells in response to chronic Ag stimulation and selectively restricts the survival of these cells, gradually pruning self-reactivity from the mature repertoire to impose a novel layer of peripheral B cell tolerance.

A case of percutaneous cryoablation complicated by subcapsular hemorrhage managed conservatively.

Herein, we report a patient who underwent percutaneous cryoablation for suspected renal cell carcinoma and developed a subcapsular hematoma with numerous pseudoaneurysms and dramatic structural deformity. Despite the severity suggested by the radiologic presentation, a conservative management approach was selected due to the patient's favorable hemodynamic status. This resulted in a positive outcome as alternative treatment options would have resulted in loss of the organ.