Adipocytes promote interleukin-18 binding to its receptors during abdominal aortic aneurysm formation in mice.

Aims: Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human and mouse AAA lesions, IL18 colocalizes to its receptors at regions rich in adipocytes, suggesting a role of adipocytes in promoting IL18 actions in AAA development.

A Jagged 1-Notch 4 molecular switch mediates airway inflammation induced by ultrafine particles.

Background: Exposure to traffic-related particulate matter promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which particulate matter exposure acts to mediate these effects remain unclear.

Objective: We sought to elucidate the cellular targets and signaling pathways critical for augmentation of allergic airway inflammation induced by ambient ultrafine particles (UFP).

The Ron Receptor Tyrosine Kinase Regulates Macrophage Heterogeneity and Plays a Protective Role in Diet-Induced Obesity, Atherosclerosis, and Hepatosteatosis.

Obesity is a chronic inflammatory disease mediated in large part by the activation of inflammatory macrophages. This chronic inflammation underlies a whole host of diseases including atherosclerosis, hepatic steatosis, insulin resistance, type 2 diabetes, and cancer, among others. Macrophages are generally classified as either inflammatory or alternatively activated.

Vehicular exhaust particles promote allergic airway inflammation through an aryl hydrocarbon receptor-notch signaling cascade.

Background: Traffic-related particulate matter (PM) has been linked to a heightened incidence of asthma and allergic diseases. However, the molecular mechanisms by which PM exposure promotes allergic diseases remain elusive.

Objective: We sought to determine the expression, function, and regulation of pathways involved in promotion of allergic airway inflammation by PM.

IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms.

Immunoglobulin E (IgE) activates mast cells (MCs). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms (AAAs). This study demonstrates that CD4+ T cells express IgE receptor FcεR1, at much higher levels than do CD8+ T cells.

CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.

Background: CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive.

CCR10 and its ligands in regulation of epithelial immunity and diseases.

Epithelial tissues covering the external and internal surface of a body are constantly under physical, chemical or biological assaults. To protect the epithelial tissues and maintain their homeostasis, multiple layers of immune defense mechanisms are required. Besides the epithelial tissue-resident immune cells that provide the first line of defense, circulating immune cells are also recruited into the local tissues in response to challenges.

Immune activation resulting from NKG2D/ligand interaction promotes atherosclerosis.

Background: The interplay between the immune system and abnormal metabolic conditions sustains and propagates a vicious feedback cycle of chronic inflammation and metabolic dysfunction that is critical for atherosclerotic progression. It is well established that abnormal metabolic conditions, such as dyslipidemia and hyperglycemia, cause various cellular stress responses that induce tissue inflammation and immune cell activation, which in turn exacerbate the metabolic dysfunction. However, molecular events linking these processes are not well understood.

Cathepsin K deficiency reduces elastase perfusion-induced abdominal aortic aneurysms in mice.

Objective: Cathepsin K (CatK) is one of the most potent mammalian elastases. We have previously shown increased expression of CatK in human abdominal aortic aneurysm (AAA) lesions. Whether this protease participates directly in AAA formation, however, remains unknown.

Cutting edge: Intrinsic programming of thymic γδT cells for specific peripheral tissue localization.

Various innate-like T cell subsets preferentially reside in specific epithelial tissues as the first line of defense. However, mechanisms regulating their tissue-specific development are poorly understood. Using the prototypical skin intraepithelial γδT cells (sIELs) as a model, we show in this study that a TCR-mediated selection plays an important role in promoting acquisition of a specific skin-homing property by fetal thymic sIEL precursors for their epidermal location, and the skin-homing potential is intrinsically programmed even before the selection.

Interleukin-2-inducible T cell kinase (Itk) network edge dependence for the maturation of iNKT cell.

Invariant natural killer T (iNKT) cells are a unique subset of innate T lymphocytes that are selected by CD1d. They have diverse immune regulatory functions via the rapid production of interferon-γ (IFN-γ) and interleukin-4 (IL-4). In the absence of signaling nodes Itk and Txk, Tec family non-receptor tyrosine kinases, mice exhibit a significant block in iNKT cell development.

CCR10 is important for the development of skin-specific gammadeltaT cells by regulating their migration and location.

Unlike conventional αβ T cells, which preferentially reside in secondary lymphoid organs for adaptive immune responses, various subsets of unconventional T cells, such as the γδ T cells with innate properties, preferentially reside in epithelial tissues as the first line of defense. However, mechanisms underlying their tissue-specific development are not well understood. We report in this paper that among different thymic T cell subsets fetal thymic precursors of the prototypic skin intraepithelial Vγ3(+) T lymphocytes (sIELs) were selected to display a unique pattern of homing molecules, including a high level of CCR10 expression that was important for their development into sIELs.

Differential roles of IL-2-inducible T cell kinase-mediated TCR signals in tissue-specific localization and maintenance of skin intraepithelial T cells.

Tissue-specific innate-like gammadelta T cells are important components of the immune system critical for the first line of defense, but mechanisms underlying their tissue-specific development are poorly understood. Our study with prototypical skin-specific intraepithelial gammadeltaT lymphocytes (sIELs) found that among different thymic gammadelta T cell subsets fetal thymic precursors of sIELs specifically acquire a unique skin-homing property after positive selection, suggesting an important role of the TCR selection signaling in "programming" them for tissue-specific development. In this study, we identified IL-2-inducible T cell kinase (ITK) as a critical signal molecule regulating the acquirement of the skin-homing property by the fetal thymic sIEL precursors.

Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production.

The Tec kinase Itk is critical for the development of alphabeta T cells as well as differentiation of CD4(+) T cells into Th2 cells. Itk null mice have defects in the production of Th2 cytokines; however, they paradoxically have significant elevations in serum IgE. Here we show that Itk null mice have increased numbers of gammadelta T cells in the thymus and spleen.

All-trans retinoic acid biases immune response induced by DNA vaccine in a Th2 direction.

Vitamin A deficiency diminishes Th2-mediated Ab responses. Providing Vitamin A or its active metabolites reverses this defect. All-trans retinoic acid (ATRA), an acid derivation of Vitamin A, regulates the balance of immune response induced by TR421-hCGbeta DNA vaccine.