Background:The bile acid receptors FXR and TGR5 have pleiotropic functions, including immune modulation. Results: Treatment of a murine model of nonalcoholic fatty liver disease (NAFLD) with a dual FXR/TGR5 agonist decreased intrahepatic inflammation and altered the immune phenotype of monocytes. Conclusion: Bile acid receptor activation improves NAFLD. Significance: These results identify potential targeting strategies for treatment of NAFLD.

A crucial component of nonalcoholic fatty liver disease (NAFLD) pathogenesis is lipid stress, which may contribute to hepatic inflammation and activation of innate immunity in the liver. However, little is known regarding how dietary lipids, including fat and cholesterol, may facilitate innate immune activation in vivo. We hypothesized that dietary fat and cholesterol drive NAFLD progression to steatohepatitis and hepatic fibrosis by altering the transcription and phenotype of hepatic macrophages. This hypothesis was tested by using RNA‐sequencing methods to characterize and analyze sort‐purified hepatic macrophage populations that were isolated from mice fed diets with varying amounts of fat and cholesterol. The addition of cholesterol to a high‐fat diet triggered hepatic pathology reminiscent of advanced nonalcoholic steatohepatitis (NASH) in humans characterized by signs of cholesterol dysregulation, generation of oxidized low‐density lipoprotein, increased recruitment of hepatic macrophages, and significant fibrosis. RNA‐sequencing analyses of hepatic macrophages in this model revealed that dietary cholesterol induced a tissue repair and regeneration phenotype in Kupffer cells (KCs) and recruited infiltrating macrophages to a greater degree than fat. Furthermore, comparison of diseased KCs and infiltrating macrophages revealed that these two macrophage subsets are transcriptionally diverse. Finally, direct stimulation of murine and human macrophages with oxidized low‐density lipoprotein recapitulated some of the transcriptional changes observed in the RNA‐sequencing study. These findings indicate that fat and cholesterol synergize to alter macrophage phenotype, and they also challenge the dogma that KCs are purely proinflammatory in NASH. Conclusion: This comprehensive view of macrophage populations in NASH indicates mechanisms by which cholesterol contributes to NASH progression and identifies potential therapeutic targets for this common disease.

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Mastitis is a benign inflammatory process of the breast with heterogeneous histopathological findings, which clinically and radiographically may mimic a mammary carcinoma. We undertook a retrospective study on 37 cases of mastitis in our institution to correlate the radiographic imaging features and the clinical presentation with the histopathological findings. Histologically, there were 21 granulomatous, 7 fibrous, 3 plasma cell, 3 lupus, 2 lymphocytic, and 1 case of acute mastitis. Radiographically, 16/25 (64%) patients with ultrasound studies showed irregular hypoechoic masses suspicious for malignancy. Clinically, 38% of patients had an associated systemic disease.

A lymphoid‐rich stroma is a common finding in salivary gland tumors. Several reports documented this association with acinic cell carcinoma (ACC). However, cytologic studies reporting this phenomenon are rare and mainly confined to sporadic single case reports. We present the cytologic features of two cases of ACCs of the parotid gland displaying a lymphoid‐rich background and discuss the cytologic differential diagnoses of this uncommon ACC variant.