Regulation of Bacteroides acidifaciens by the aryl hydrocarbon receptor in IL-22-producing immune cells has sex-dependent consequential impact on colitis.

Introduction: Colitis is an inflammatory bowel disease (IBD) characterized by immune cell dysregulation and alterations in the gut microbiome. In our previous report, we showed a natural product in cruciferous vegetables and ligand of the aryl hydrocarbon receptor (AhR), indole-3-carbinol (I3C), was able to reduce colitis-induced disease severity and microbial dysbiosis in an interleukin-22 (IL-22) dependent manner. Methods: In the current study, we performed single-cell RNA sequencing (scRNAseq) from colonocytes during colitis induction and supplementation with I3C and show how this treatment alters expression of genes involved in IL-22 signaling. To further define the role of IL-22 signaling in I3C-mediated protection during colitis and disease-associated microbial dysbiosis, we generated mice with AhR deficiency in RAR-related orphan receptor c (Rorc)-expressing cells (AhR ΔRorc ) which depletes this receptor in immune cells involved in production of IL-22. Colitis was induced in wildtype (WT), AhR ΔRorc , and littermate (LM) mice with or without I3C treatment. Results: Results showed AhR ΔRorc mice lost the efficacy effects of I3C treatment which correlated with a loss of ability to increase IL-22 by innate lymphoid type 3 (ILC3s), not T helper 22 (Th22) cells. 16S rRNA microbiome profiling studies showed AhR ΔRorc mice were unable to regulate disease-associated increases in Bacteroides, which differed between males and females. Lastly, inoculation with a specific disease-associated Bacteroides species, Bacteroides acidifaciens (B. acidifaciens), was shown to exacerbate colitis in females, but not males. Discussion: Collectively, this report highlights the cell and sex-specific role of AhR in regulating microbes that can impact colitis disease.

Increased incidence of leukemia in patients with obstructive sleep apnea: Results from the national insurance claim data 2007-2014.

PURPOSE: Prior research suggests a link between obstructive sleep apnea (OSA) and the likelihood of developing a variety of solid tumors; however, there are no studies assessing OSA and leukemia. This study is the first to identify a potential association between OSA and leukemia using data from the Korea National Health Insurance Service database. METHODS: A total of 162,646 patients (≥20 years of age and without any cancer history) newly diagnosed with OSA between 2011 and 2017 were included. A control group of 813,230 subjects was selected using propensity score matching based on age and sex. The mean follow-up time was 4.4 ± 2.0 years. The primary endpoint was newly diagnosed leukemia of any type. The leukemia hazard ratio (95% confidence interval [CI]) was calculated for patients with OSA and compared with that of patients in the control group. RESULTS: The incidence of leukemia among patients with OSA was significantly higher than that in the controls (1.35 [1.05-1.74]). The hazard ratio was the highest, 1.74 in those under 40 years, and gradually decreased with age, to 1.38 in those aged 40-65 years and 0.96 in those over 65. In particular, the incidence of lymphoid leukemia (2.06 [1.18-3.60]) was higher than that of myeloid (1.34 [1.00-1.81]) or unspecified leukemia (0.60 [0.20-1.58]). CONCLUSION: OSA is associated with an increased incidence of leukemia, particularly in patients younger than 40 years of age.

Contributions of innate type 2 inflammation to adipose function.

A critical contributor to the health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function is altered in obesity-related disease, white AT is marked by progressive inflammation and adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts seeking interventions to mitigate obesity-associated AT inflammation continue, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed that an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g., beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally, we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology.