Summary
CD4+ T‐helper cells regulate immunity and inflammation through the acquisition of potential to secrete specific cytokines. The acquisition of cytokine‐secreting potential, in a process termed ...T‐helper cell differentiation, is a response to multiple environmental signals including the cytokine milieu. The most recently defined subset of T‐helper cells are termed Th9 and are identified by the potent production of interleukin‐9 (IL‐9). Given the pleiotropic functions of IL‐9, Th9 cells might be involved in pathogen immunity and immune‐mediated disease. In this review, I focus on recent developments in understanding the signals that promote Th9 differentiation, the transcription factors that regulate IL‐9 expression, and finally the potential roles for Th9 cells in immunity in vivo.
Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and ...retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.
Cu is an essential micronutrient, and its role in an array of critical physiological processes is receiving increasing attention. Among these are wound healing, angiogenesis, protection against ...reactive oxygen species, neurotransmitter synthesis, modulation of normal cell and tumor growth, and many others. Free Cu is absent inside cells, and a network of proteins has evolved to deliver this essential, but potentially toxic, metal ion to its intracellular target sites following uptake. Although the total body content is low (∼100 mg), dysfunction of proteins involved in Cu homeostasis results in several well-characterized human disease states. The initial step in cellular Cu handling is its transport across the plasma membrane, a subject of study for only about the last 25 years. This review focuses on the initial step in Cu homeostasis, the properties of the major protein, hCTR1, that mediates Cu uptake, and the status of our understanding of this highly specialized transport system. Although a high-resolution structure of the protein is still lacking, an array of biochemical and biophysical studies have provided a picture of how hCTR1 mediates Cu(I) transport and how Cu is delivered to the proteins in the intracellular milieu. Recent studies provide evidence that the transporter also plays a key protective role in the regulation of cellular Cu via regulatory endocytosis, lowering its surface expression, in response to elevated Cu loads.
Antigen-Presenting Cells in the Skin Kashem, Sakeen W; Haniffa, Muzlifah; Kaplan, Daniel H
Annual review of immunology,
04/2017, Volume:
35, Issue:
1
Journal Article
Peer reviewed
Open access
Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, ...patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen-sensing, -processing, and -presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation. Skin APCs are a highly heterogeneous population with functionally specialized subsets that are developmentally imprinted and modulated by local tissue microenvironmental and inflammatory cues. This review explores recent advances that have allowed for a more accurate taxonomy of APC subsets found in both mouse and human skin. It also examines the functional specificity of individual APC subsets and their collaboration with other immune cell types that together promote adaptive T cell and regional cutaneous immune responses during homeostasis, inflammation, and disease.
A brief history of IL-9 Goswami, Ritobrata; Kaplan, Mark H
The Journal of immunology (1950),
2011-Mar-15, 2011-03-15, 20110315, Volume:
186, Issue:
6
Journal Article
Peer reviewed
Open access
IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system. Although many biological functions have been attributed to ...IL-9, it remains an understudied cytokine. A resurgence of interest in IL-9 has been spurred by recent work demonstrating a role for IL-9 in regulating inflammatory immunity and defining the transcription factors that activate the Il9 gene in cells that most efficiently produce IL-9. In this review, we summarize the characterization of IL-9 biological activities, highlight roles for the cytokine that are clearly defined, and outline questions regarding IL-9 functions that still require further exploration.
Copper (Cu) is an essential micronutrient but excess Cu is potentially toxic. Its important propensity to cycle between two oxidation states accounts for its frequent presence as a cofactor in many ...physiological processes through Cu-containing enzymes, including mitochondrial energy production (via cytochrome c-oxidase), protection against oxidative stress (via superoxide dismutase), and extracellular matrix stability (via lysyl oxidase). Since free Cu is potentially toxic, the bioavailability of intracellular Cu is tightly controlled by Cu transporters and Cu chaperones. Recent evidence reveals that these Cu transport systems play an essential role in the physiological responses of cardiovascular cells, including cell growth, migration, angiogenesis and wound repair. In response to growth factors, cytokines, and hypoxia, their expression, subcellular localization, and function are tightly regulated. Cu transport systems and their regulators have also been linked to various cardiovascular pathophysiologies such as hypertension, inflammation, atherosclerosis, diabetes, cardiac hypertrophy, and cardiomyopathy. A greater appreciation of the central importance of Cu transporters and Cu chaperones in cell signaling and gene expression in cardiovascular biology offers the possibility of identifying new therapeutic targets for cardiovascular disease.
In the past few years there has been an explosion in the characterization of skin-resident dendritic cells (DCs). This is largely because of the development of several lines of mice with genetic ...alterations that allow for selective targeting of many of these subsets. There are now considerable data derived from in vivo experiments using these mice. This review focuses on the relative contribution of murine skin-resident DCs in the generation of immune responses to epicutaneous application of ovalbumin and during contact hypersensitivity. We describe a model in which the two best-characterized skin-resident DCs, langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) have distinct functions: Langerin+ dDCs initiate and LCs suppress T cell responses.
Innate resistance to Candida albicans in mucosal tissues requires the production of interleukin-17A (IL-17A) by tissue-resident cells early during infection, but the mechanism of cytokine production ...has not been precisely defined. In the skin, we found that dermal γδ T cells were the dominant source of IL-17A during C. albicans infection and were required for pathogen resistance. Induction of IL-17A from dermal γδ T cells and resistance to C. albicans required IL-23 production from CD301b+ dermal dendritic cells (dDCs). In addition, we found that sensory neurons were directly activated by C. albicans. Ablation of sensory neurons increased susceptibility to C. albicans infection, which could be rescued by exogenous addition of the neuropeptide CGRP. These data define a model in which nociceptive pathways in the skin drive production of IL-23 by CD301b+ dDCs resulting in IL-17A production from γδ T cells and resistance to cutaneous candidiasis.
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•γδ T cell production of IL-17A inhibits cutaneous Candida albicans infection•CD301b+ dDC production of IL-23 drives IL-17A production by dermal γδ T cells•Sensory neurons directly sense C. albicans and augment IL-23 production•CGRP from TRPV1-positive fibers drives IL-23 production from CD301b+ dDCs
The cellular network involved in innate resistance to C. albicans is poorly described. In this study, Kaplan and colleagues find that sensory neurons detect C. albicans and release CGRP to drive IL-23 production from dermal CD301b+ DCs that then elicits protective IL-17 production from dermal γδ T cells.
BIOCHEMISTRY OF NA,K-ATPASE Kaplan, Jack H
Annual review of biochemistry,
01/2002, Volume:
71, Issue:
1
Journal Article
Peer reviewed
The Na,K-ATPase or sodium pump carries out the coupled extrusion and uptake
of Na and K ions across the plasma membranes of cells of most higher
eukaryotes. It is a member of the P-type ATPase ...superfamily. This heterodimeric
integral membrane protein is composed of a 100-kDa α-subunit with ten
transmembrane segments and a heavily glycosylated β subunit of about 55
kDa, which is a type II membrane protein. Current ideas on how the protein
achieves active transport are based on a fusion of results of transport
physiology, protein chemistry, and heterologous expression of mutant proteins.
Recently acquired high resolution structural information provides an important
new avenue for a more complete understanding of this protein. In this review,
the current status of knowledge of Na,K-ATPase is discussed, and areas where
there is still considerable uncertainty are highlighted.
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