International journal of basic and clinical immunology最新文献

Eosinophilia may be responsible for cardiac injuries of widely varying severity, from acute myocarditis to endomyocardial fibrosis. In this manuscript, we present both the molecular and physiological evidence that promotes eosinophils accumulation in mice heart epicardium and myocardium region of allergen or transgene-insertion of overexpressed IL-15, eotaxin-deficient CD2 promoter driven IL-5 transgenic mice shows abnormal physiological function. Numerous etiologies can lead to severe eosinophilia, but these are mainly represented by hypersensitivity reactions, rheumatological diseases and hypereosinophilic syndrome. Because cardiac involvement may be extremely severe; therefore, we even present echocardiography analysis that indicates IL-15 overexpressed mice showed induced blood eosinophilia associated progression of cardiac abnormalities.

We recently rereported that blood mRNA levels of T cells and IgE receptors are the novel non-invasive biomarkers for eosinophilic esophagitis (EoE) with the aim to establish the panel of T cells and IgE receptor as the novel non-invasive biomarkers for EoE. In addition to earlier proposed cell surface molecules, we now added T cell receptor CXCR6 and eosinophils expressed cell surface molecules CD101 and CD274 mRNA levels. The mRNA levels of eosinophils cell surface molecule CD101 and CD274 and T cell receptor CXCR6, Vβ11, CD1d and chemokine CXCL16 levels were examined using the blood of normal, EoE and GERD patients. The analysis showed statistically significant induced mRNA levels of CD274, CD101 and reduced CXCR6 will be an additional molecule with respective 95%, 90% and 90% positive predictive value in between EoE and GERD patients. In brief, these additional data will be critical to establish a complete panel of earlier published TCRδ (95%), Jα18 (83%) and FCεRII (100%) non-invasive biomarker to monitor the EoE severity and treatment effect in EoE patients. In conclusion, we now propose both induced and reduced transcript levels of cell surface molecules of the cell surface molecules along with earlier reported molecules that will be useful for monitoring EoE status before and following treatment. Most importantly, the complete predictive non-invasive biomarker panel will also serve to differentiate EoE from GERD.

Objectives: Pancreatic malignancy is a major public health problem worldwide and recent reports indicated that pancreatic cancer will be second most common cause of cancer-related deaths by the end of 2021. The cause of increasing death rate is due to the nonexistence of detection tools to early diagnose, poor prognosis, resistance to chemotherapy and also lack in understanding the mechanism of PDAC pathogenesis. Circulating tumor cells (CTCs) play a major role in metastatic step of intravasation and presence of these cells are strong prognostic marker for the progression of pancreatic malignancy in chronic pancreatitis (CP).

Goal: Identifying the novel CTCs in the chronic inflammation mediated experimental model for the progression of malignancy in CP.

Methods: We have performed flow cytometer and immunofluorescence analyses in the lymphoid and lung samples was performed o detect CTCs in the chronic inflammation induced mouse model CP.

Results: We report that induced SOX9 positive cells were observed in the blood, lymph node and spleen samples of cerulein with azoximethane (AOM) treated mouse model of CP compared to cerulein alone. Further, we provide evidence that early metastasis through the migration and homing of mega merged SOX9⁺ and PDX⁺ ductal stem cells (CTCs) in the lungs of cerulein with AOM treated mice. These identified CTCs in experimentally induced malignant pancreatitis may serve as a novel finding to identify a non-invasive biomarker that needs to be examined in the blood of human pancreatic cancer.

Conclusions: Taken together, the presented data of identified mega merged SOX9⁺ and PDX⁺ ductal stem cells (CTCs) may serve a non-invasive biomarker for the early detection of pancreatic malignancy and metastasis.

Background and aim: IgE-mediated immune responses contribute to the pathogenesis of eosinophilic esophagitis (EoE). Interleukin (IL)-4 is a well-established cytokine involved in B cell activation, immunoglobulin (Ig) E production and isotype class switching. Earlier reports indicated that IL-15, B cells and IgE are induced in EoE pathogenesis. Therefore, we hypothesized that induced IL-15 and IgE may have a significant correlation in promoting EoE pathogenesis.

Methods: Accordingly, we performed ELISA, qPCR, flowcytometric and immunostaining analyses to examine IgE, B cells, eosinophils and mast cells in the esophagus of IL-15 overexpressed mice following EoE induction.

Results: Herein, we show that IL-15 overexpressed mice indeed have induced baseline IL-4, B cells, eosinophils, mast cells and IgE levels in the blood and esophagus. Further, we observed that IL-15 overexpressed mice show induction of IgE, and accumulation of degranulated eosinophils and mast cells in allergen-induced experimental EoE. Notably, despite induced blood IgE, esophageal eosinophilia is not induced in intestinal fatty acid binding protein IL-15 overexpressed gene (Fabpi-IL-15) mice. Fabpi-IL-15 transgenic mice showed IgE in the blood and intestine and intestinal eosinophilia, but no esophageal eosinophilia at baseline and comparable eosinophils in the esophagus of saline and allergen challenged Fabpi-IL-15 mice. Similarly, allergen challenged IL-15 gene-deficient mice show reduced IgE and esophageal eosinophilia in allergen-induced experimental EoE.

Conclusions: Taken together, we for the first time provide direct evidence that tissue-specific IL-15 induced IgE mediated responses, not systemic IgE is critical in promoting EoE pathogenesis.