ABSTRACT
Chronic tissue inflammation often results in fibrosis characterized by the accumulation of extracellular matrix components remodeling normal tissue architecture and function. Recent studies have suggested common immune mechanisms despite the complexity of the interactions between tissue-specific fibroblasts, macrophages, and distinct immune cell populations that mediate fibrosis in various tissues. Natural killer T (NKT) cells recognizing lipid antigens bound to CD1d molecules have been shown to play an important role in chronic inflammation and fibrosis. Here we review recent data in both experimental models and in humans that suggest a key role of type 1 invariant NKT (iNKT) cell activation in the progression of inflammatory cascades leading to recruitment of neutrophils and activation of the inflammasome, macrophages, fibroblasts, and, ultimately, fibrosis. Emerging evidence suggests that iNKT-associated mechanisms contribute to type 1, type 2 and type 3 immune pathways mediating tissue fibrosis, including idiopathic pulmonary fibrosis (IPF). Thus, targeting a pathway upstream of these immune mechanisms, such as the inhibition of iNKT activation, may be important in modulating various fibrotic conditions.
Subject(s)
Natural Killer T-Cells , Humans , Inflammation , Fibrosis , Antigens, CD1d , Lymphocyte ActivationABSTRACT
Oral sedation with benzodiazepines and anxiolysis with nitrous oxide are 2 effective methods to help alleviate anxiety and fear of dental procedures. Many patients would prefer to have their dentistry performed with sedation if it were offered to them. This article presents a detailed discussion on minimal sedation that should give the reader a good understanding of this valuable aspect of clinical care.
Subject(s)
Dental Anxiety/prevention & control , Dental Care/psychology , Adult , Anesthesia, Inhalation/instrumentation , Anesthesiology/education , Anesthesiology/legislation & jurisprudence , Anesthetics, Inhalation/administration & dosage , Anti-Anxiety Agents/therapeutic use , Benzodiazepines/antagonists & inhibitors , Benzodiazepines/therapeutic use , Child , Conscious Sedation/methods , Education, Dental/legislation & jurisprudence , Humans , Hypnotics and Sedatives/administration & dosage , Medical History Taking , Monitoring, Physiologic , Nitrous Oxide/administration & dosage , Patient Care Planning , Risk Assessment , United StatesABSTRACT
Receptor editing is a mode of immunological tolerance of B lymphocytes that involves antigen-induced B-cell receptor signaling and consequent secondary immunoglobulin light chain gene recombination. This ongoing rearrangement often changes B-cell specificity for antigen, rendering the cell non-autoreactive and sparing it from deletion. We currently believe that tolerance-induced editing is limited to early stages in B-cell development and that it is a major mechanism of tolerance, with a low-affinity threshold and the potential to take place in virtually every developing B cell. The present review highlights the contributions from our laboratory over several years to elucidate these features.
