Search results for "81"
showing 10 items of 2468 documents
The cAMP pathway as therapeutic target in autoimmune and inflammatory diseases
2016
Nucleotide signaling molecules contribute to the regulation of cellular pathways. In the immune system, cyclic adenosine monophosphate (cAMP) is well established as a potent regulator of innate and adaptive immune cell functions. Therapeutic strategies to interrupt or enhance cAMP generation or effects have immunoregulatory potential in autoimmune and inflammatory disorders. Here, we provide an overview of the cyclic AMP axis and its role as a regulator of immune functions and discuss the clinical and translational relevance of interventions with these processes.
Human Vδ1+ T Cells in the Immune Response to Plasmodium falciparum Infection
2019
Naturally acquired protective immunity to Plasmodium falciparum malaria is mainly antibody-mediated. However, other cells of the innate and adaptive immune system also play important roles. These include so-called unconventional T cells, which express a γδ T-cell receptor (TCR) rather than the αβ TCR expressed by the majority of T cells-the conventional T cells. The γδ T-cell compartment can be divided into distinct subsets. One expresses a TCR involving Vγ9 and Vδ2, while another major subset uses instead a TCR composed of Vδ1 paired with one of several types of γ chains. The former of these subsets uses a largely semi-invariant TCR repertoire and responds in an innate-like fashion to pyro…
γδ T Cells and Tumor Microenvironment: From Immunosurveillance to Tumor Evasion.
2018
gamma delta T cells possess cytotoxic antitumor activity mediated by production of proinflammatory cytokines, direct cytotoxic activity, and regulation of the biological functions of other cell types. Hence, these features have prompted the development of therapeutic strategies in which gamma delta T cells agonists or ex vivo-expanded gamma delta T cells are administered to tumor patients. Several studies have shown that gamma delta T cells are an important component of tumor-infiltrating lymphocytes in patients affected by different types of cancer and a recent analysis of similar to 18,000 transcriptomes from 39 human tumors identified tumor-infiltrating.d T cells as the most significant …
Myeloid-Derived Suppressor Cells Specifically Suppress IFN-γ Production and Antitumor Cytotoxic Activity of Vδ2 T Cells.
2018
γδ T cells represent less than 5% of circulating T cells; they exert a potent cytotoxic function against tumor or infected cells and secrete cytokines like conventional αβ T cells. As αβ T cells γδ T cells reside in the typical T cell compartments (the lymph nodes and spleen), but are more widely distributed in tissues throughout the body. For these reasons, some investigators are exploring the possibility of immunotherapies aimed to expand and activate Vδ2 T cells, or using them as Chimeric Antigen Receptor carriers. However, the role of immunosuppressive microenvironment on Vδ2 T cells during infections and cancers has not been completely elucidated. In particular, the effects of myeloid-…
Fungal Deoxynivalenol-Induced Enterocyte Distress Is Attenuated by Adulterated Adlay: In Vitro Evidences for Mucoactive Counteraction
2018
Adlay is a cereal crop that has long been used as traditional herbal medicine and as a highly nourishing food. However, deoxynivalenol (DON), the most prevalent trichothecene mycotoxin worldwide, frequently spoils grains, including adlay, via fungal infection. On the basis of an assumption that the actions of DON in the gut could be modified by adlay consumption, we simulated the impacts of co-exposure in enterocytes and investigated the effectiveness of treatment with adlay for reducing the risk of DON-induced inflammation and epithelia barrier injury. In particular, adlay suppressed DON-induced pro-inflammatory signals such as mitogen-activated kinase transduction and the epidermal growth…
Cyclic AMP Represents a Crucial Component of Treg Cell-Mediated Immune Regulation
2016
T regulatory (Treg) cells are one of the key players in the immune tolerance network, and a plethora of manuscripts have described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate as to which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP), which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted, the source and the mechanism of action of cAMP are less clear, and a multitude of seemingly contradictory data allow for, in principle, tw…
Characterization of zolbetuximab in pancreatic cancer models
2018
ABSTRACT In healthy tissue, the tight junction protein Claudin 18.2 (CLDN18.2) is present only in the gastric mucosa. Upon malignant transformation of gastric epithelial tissue, perturbations in cell polarity lead to cell surface exposure of CLDN18.2 epitopes. Moreover, CLDN18.2 is aberrantly expressed in malignancies of several other organs, such as pancreatic cancer (PC). A monoclonal antibody, zolbetuximab (formerly known as IMAB362), has been generated against CLDN18.2. In a phase 2 clinical trial (FAST: NCT01630083), zolbetuximab in conjunction with chemotherapy prolonged overall and progression-free survival over chemotherapy alone and improved quality of life. In this study, the mech…
Update of Immunosenescence in Cerebral Small Vessel Disease
2020
Aging of the central nervous system (CNS) is closely associated with chronic sterile low-grade inflammation in older organisms and related immune response. As an amplifier for neuro-inflammaging, immunosenescence remodels and deteriorates immune systems gradually with the passage of time, and finally contributes to severe outcomes like stroke, dementia and neurodegeneration in elderly adults. Cerebral small vessel disease (CSVD), one of the major causes of vascular dementia, has an intensive connection with the inflammatory response and immunosenescence plays a crucial role in the pathology of this disorder. In this review, we discuss the impact of immunosenescence on the development of CSV…
Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is mediated by NK cells.
2017
ABSTRACT The B16F10 murine melanoma cell line displays a low expression of MHC class I molecules favoring immune evasion and metastases in immunocompetent C57 BL/6 wild-type mice. Here, we generated metastases to the liver, an organ that is skewed towards immune tolerance, by intrasplenic injection of B16F10 cells in syngeneic C57 BL/6 compared to allogeneic Balb/c mice. Surprisingly, Balb/c mice, which usually display a pronounced M2 macrophage and Th2 T cell polarization, were ∼3 times more susceptible to metastasis than C57 BL/6 mice, despite a much higher M1 and Th1 T cell immune response. The anti-metastatic advantage of C57 BL/6 mice could be attributed to a more potent NK-cell mediat…
RNase H2 Loss in Murine Astrocytes Results in Cellular Defects Reminiscent of Nucleic Acid-Mediated Autoinflammation
2018
Aicardi-Goutières syndrome (AGS) is a rare early onset childhood encephalopathy caused by persistent neuroinflammation of autoimmune origin. AGS is a genetic disorder and >50% of affected individuals bear hypomorphic mutations in ribonuclease H2 (RNase H2). All available RNase H2 mouse models so far fail to mimic the prominent CNS involvement seen in AGS. To establish a mouse model recapitulating the human disease, we deleted RNase H2 specifically in the brain, the most severely affected organ in AGS. Although RNase H2δGFAPmice lacked the nuclease in astrocytes and a majority of neurons, no disease signs were apparent in these animals. We additionally confirmed these results…