Heterogeneity of ILC2s in the Intestine; Homeostasis and Pathology.

Group 2 innate lymphoid cells (ILC2s) were identified in 2010 as a novel lymphocyte subset lacking antigen receptors, such as T-cell or B-cell receptors. ILC2s induce local immune responses characterized by producing type 2 cytokines and play essential roles for maintaining tissue homeostasis. ILC2s are distributed across various organs, including the intestine where immune cells are continuously exposed to external antigens. Followed by luminal antigen stimulation, intestinal epithelial cells produce alarmins, such as IL-25, IL-33, and thymic stromal lymphopoietin, and activate ILC2s to expand and produce cytokines. In the context of parasite infection, the tuft cell lining in the epithelium has been revealed as a dominant source of intestinal IL-25 and possesses the capability to regulate ILC2 homeostasis. Neuronal systems also regulate ILC2s through neuropeptides and neurotransmitters, and interact with ILC2s bidirectionally, a process termed "neuro-immune crosstalk". Activated ILC2s produce type 2 cytokines, which contribute to epithelial barrier function, clearance of luminal antigens and tissue repair, while ILC2s are also involved in chronic inflammation and tissue fibrosis. Recent studies have shed light on the contribution of ILC2s to inflammatory bowel diseases, mainly comprising ulcerative colitis and Crohn's disease, as defined by chronic immune activation and inflammation. Modern single-cell analysis techniques provide a tissue-specific picture of ILC2s and their roles in regulating homeostasis in each organ. Particularly, single-cell analysis helps our understanding of the uniqueness and commonness of ILC2s across tissues and opens the novel research area of ILC2 heterogeneity. ILC2s are classified into different phenotypes depending on tissue and phase of inflammation, mainly inflammatory and natural ILC2 cells. ILC2s can also switch phenotype to ILC1- or ILC3-like subsets. Hence, recent studies have revealed the heterogeneity and plasticity of ILC2, which indicate dynamicity of inflammation and the immune system. In this review, we describe the regulatory mechanisms, function, and pathological roles of ILC2s in the intestine.

[Transudative chylothorax complicated with liver cirrhosis due to primary biliary cholangitis:case report].

A 70-year-old woman who was diagnosed with liver cirrhosis as a result of primary biliary cholangitis and heart failure by myocardial infarction 1 month ago complained of dyspnea and was admitted to our hospital. Image inspections showed right massive pleural effusion, so we performed thoracentesis and drainage. Despite no history of trauma or malignancy, we obtained milky white-yellow pleural effusion by drainage and it turned out to be transudative chylothorax. Because there were no signs of heart failure exacerbation or other diseases, we suspected that the transudative chylothorax was caused by liver cirrhosis. For cardioprotection and improvement of portal hypertension, we used conservative treatments such as increasing diuretic dosage, inducing branched-chain amino acids, and switching ß-blocker medication from bisoprolol to carvedilol. Even though thoracentesis and drainages were performed twice for improvement of hypoxemia, right pleural effusion gradually decreased with the disappearance of dyspnea and she was discharged from our hospital on the 20th hospital day. We have been following her for 10 months and have found no evidence of pleural effusion. Although liver cirrhosis complicated with chylothorax is rare, several case reports have shown all patients with chylothorax caused by liver cirrhosis were transudative. It is assumed that portal hypertension by liver cirrhosis is associated with transudative chylothorax. This patient's case is complicated by insufficient ascites to be punctured. Other studies have reported that chylothorax occurs as a result of chylous ascites passing through the diaphragm in patients with liver cirrhosis;however, our case does not appear to fit the mechanism. Another study has proposed that portal hypertension increased lymph fluid production in the liver, this flow in the thoracic duct, and increased intrathoracic pressure resulting in the occurrence of chylothorax. We believe that switching ß-blocker medication from bisoprolol to carvedilol is one of the reasons this patient's right chylothorax gradually decreased. According to one case study, a nonselective ß-blocker improves chylothorax by lowering portal hypertension. As a result, a nonselective ß-blocker such as carvedilol that improves portal hypertension may contribute to a reduction in cirrhotic chylothorax in this case. Bisoprolol, a selective ß-blocker, has no effects on portal pressure and intrathoracic pressure. Our case report suggests that portal hypertension causes transudative chylothorax complicated by liver cirrhosis and that medication for portal hypertension improvement, such as a nonselective ß-blocker, is one option for treatment.