The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident innate immune cells to produce substantial quantities of IFN-γ. We identified CD161Bright mucosal-associated invariant T (MAIT) and CD56Bright NK cells as the responding liver-resident innate immune cells. Their activation was not directly induced by the TLR8 agonist but was dependent on IL-12 and IL-18 production by ssRNA40-activated intrahepatic monocytes. Importantly, the ssRNA40-induced cytokine-dependent activation of MAIT cells mirrored responses induced by bacteria, i.e., generating a selective production of high levels of IFN-γ, without the concomitant production of TNF-α or IL-17A. The intrahepatic IFN-γ production could be detected not only in healthy livers, but also in HBV- or HCV-infected livers. In conclusion, the human liver harbors a network of immune cells able to modulate their immunological responses to different pathogen-associated molecules. Their ability to generate a strong production of IFN-γ upon stimulation with TLR8 agonist opens new therapeutic opportunities for the treatment of diverse liver pathologies.

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Highlights GM-CSF and TNFa producing CD206 + macrophages accumulate in human fibrotic liver Serum GM-CSF is increased in HCV + patients with higher liver fibrosis GM-CSF drives monocyte to CD206 + macrophage conversion Anti-GM-CSF therapy suppresses liver fibrosis and CD206 + macrophage accumulation Lay summary Liver fibrosis is a major driver of liver disease progression. Herein, we have shown that granulocytemacrophage colony-stimulating factor (GM-CSF) plays an important role in the development of liver fibrosis. Our findings support the use of anti-GM-CSF neutralising antibodies for the management of patients with chronic liver disease resulting from both viral and non-viral causes.

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Pancreatic lymphangiomas are very rare benign cystic lesions that pose a diagnostic dilemma due to their resemblance to other nonneoplastic and neoplastic pancreatic cystic lesions. As such, pancreatic lymphangiomas are frequently diagnosed only after histological examination of the excised lesion. We present 2 cases of pancreatic lymphangioma, determine its prevalence at our institution and perform a detailed review of published literature since 2010. Case 1 is a 36-year-old male and case 2 is a 35-year-old female, both of which presented with abdominal pain. These were the only cases of pancreatic lymphangiomas reported at our institution since 2010. We reviewed 69 cases of pancreatic lymphangiomas from 52 publications. It affects predominantly females with a median age of 43 and such patients typically present with abdominal pain (58.8%) or are asymptomatic (27.9%). The median size is 8.6 cm, the most common location is the head of pancreas and the most common imaging finding is that of a multilocular cyst. Majority of patients underwent surgical resection (69.6%). Endoscopic ultrasound-guided fine-needle aspiration features of pancreatic lymphangiomas include chylous cyst fluid, elevated fluid triglyceride levels (15/16 cases) and numerous lymphocytes on cytology. The majority of patients with elevated fluid triglyceride levels (13/15 cases) were managed conservatively. Pancreatic lymphangiomas are rare pancreatic cystic lesions that may be diagnosed preoperatively using a multidisciplinary and multimodal approach involving clinical, radiological, biochemical and cytological features, allowing greater confidence in the selection of patients who can be managed conservatively.