Annexin V expression on CD4 T cells with regulatory function.

Regulatory T (Treg) cells induce immunologic tolerance by suppressing effector functions of conventional lymphocytes in the periphery. On the other hand, immune silencing is mediated by recognition of phosphatidylserine (PS) on apoptotic cells by phagocytes. Here we describe expression of the PS-binding protein Annexin V (ANXA5) in CD4  CD25 Treg cells at the mRNA and protein levels.

Chemoattractant Signals and Adhesion Molecules Promoting Human Regulatory T Cell Recruitment to Porcine Endothelium.

Background: Human CD4+CD25+Foxp3+ T regulatory cells (huTreg) suppress CD4+ T cell-mediated antipig xenogeneic responses in vitro and might therefore be used to induce xenograft tolerance. The present study investigated the role of the adhesion molecules, their porcine ligands, and the chemoattractant factors that may promote the recruitment of huTreg to porcine aortic endothelial cells (PAEC) and their capacity to regulate antiporcine natural killer (NK) cell responses.

Methods: Interactions between ex vivo expanded huTreg and PAEC were studied by static chemotaxis assays and flow-based adhesion and transmigration assays.

Contact with stimulated T cells up-regulates expression of peptidylarginine deiminase 2 and 4 by human monocytes.

Objective: The antigenic targets of the rheumatoid arthritis (RA)-associated autoantibodies to "citrullinated" proteins are generated following citrullination by a peptidylarginine deiminase (PAD). Of the five PAD isotypes, two - PAD2 and PAD4 - are expressed in RA synovial tissue. Within this tissue, the activation of macrophages and fibroblasts mediated by T-cell contact or driven by cytokines plays a prominent part in the pathogenesis.

In vivo dioxin favors interleukin-22 production by human CD4+ T cells in an aryl hydrocarbon receptor (AhR)-dependent manner.

Background: The transcription factor aryl hydrocarbon receptor (AhR) mediates the effects of a group of chemicals known as dioxins, ubiquitously present in our environment. However, it is poorly known how the in vivo exposure to these chemicals affects in humans the adaptive immune response. We therefore assessed the functional phenotype of T cells from an individual who developed a severe cutaneous and systemic syndrome after having been exposed to an extremely high dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells.

Ligands of the aryl hydrocarbon receptor (AHR), a transcription factor mediating the effects of dioxin, favor Th17 differentiation and exacerbate autoimmunity in mice. We investigated how AHR ligands affected human T-cell polarization. We found that the high affinity and stable AHR-ligand dioxin as well as the natural AHR-ligand 6-formylinolo[3,2-b] carbazole induced the downstream AHR-target cytochrome P450A1, and without affecting IFN-gamma, they enhanced IL-22 while simultaneously decreasing IL-17A production by CD4(+) T cells.

Inhibition of T cell-dependent and RANKL-dependent osteoclastogenic processes associated with high levels of bone mass in interleukin-15 receptor-deficient mice.

Objective: T cell production of RANKL, interferon-γ (IFNγ), and other cytokines in inflammatory processes such as rheumatoid arthritis or secondary to conditions such as estrogen deficiency stimulates osteoclast activity, which leads to bone resorption and bone loss. The purpose of this study was to characterize the effects of interleukin-15 (IL-15), a master T cell growth factor whose role in bone remodeling remains unknown.

Methods: We used mice lacking the IL-15 receptor (IL-15Rα(-/-) ) to investigate the effects of IL-15 on osteoclast development, T cell and dendritic cell activation in vitro and in vivo, bone mass, and microarchitecture in intact and ovariectomized (OVX) mice.

Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion.

Microenvironment molecular cues direct T helper (Th) cell differentiation; however, Th17 fate determination is still imprecisely understood in humans. To assess the role of prostaglandin E(2) (PGE(2)) in Th expansion, we activated peripheral blood mononuclear cells by CD3 cross-linking. In the presence of exogenous PGE(2), peripheral blood mononuclear cells produced higher interleukin-17 (IL-17), C-C chemokine ligand 20 (CCL20)/macrophage inflammatory protein 3alpha (MIP-3alpha), CXC chemokine ligand 8 (CXCL8)/IL-8, and lower interferon-gamma and IL-22 levels than in control cultures.

IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes.

IL-21 is a key T-cell growth factor (TCGF) involved in innate and adaptive immune response. It contributes to the proliferation of naive, but not memory T lymphocytes. However, the full spectrum of IL-21 activity on T cells remains unclear.

Adipose tissue has anti-inflammatory properties: focus on IL-1 receptor antagonist (IL-1Ra).

The formation of adipose tissue could result from abnormal metabolic processes and, at the local level, from chronic inflammatory processes such as those occurring in the synovial cavity in rheumatoid arthritis or osteoarthritis, or the peritoneal cavity in various inflammatory processes of the digestive system. Adipocytes are said to produce many hormones and proinflammatory mediators. So far, however, little attention has been paid to cytokine inhibitory molecules.

The period length of fibroblast circadian gene expression varies widely among human individuals.

Mammalian circadian behavior is governed by a central clock in the suprachiasmatic nucleus of the brain hypothalamus, and its intrinsic period length is believed to affect the phase of daily activities. Measurement of this period length, normally accomplished by prolonged subject observation, is difficult and costly in humans. Because a circadian clock similar to that of the suprachiasmatic nucleus is present in most cell types, we were able to engineer a lentiviral circadian reporter that permits characterization of circadian rhythms in single skin biopsies.

Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue.

Adipose tissue is the source of production and site of action of several pro- and antiinflammatory cytokines. We have recently shown that white adipose tissue (WAT) is a major producer of the antiinflammatory IL-1 receptor antagonist (IL-1Ra). Because IL-1Ra serum levels are elevated 7-fold in human obesity and an excess of this protein has been implicated in the acquired resistance to leptin and insulin, we investigated the regulation of IL-1Ra in human WAT.

Production of intracellular IL-1alpha, IL-1beta, and IL-1Ra isoforms by activated human dermal and synovial fibroblasts: phenotypic differences between human dermal and synovial fibroblasts.

We compared the production of IL-1alpha, IL-1beta, and of IL-1Ra isoforms by cultured human dermal (HDF) and synovial fibroblasts (HSF) in response to IL-1alpha, TNF-alpha, or direct T cell membrane contact. IL-1Ra was constitutively present in the cell lysates of cultured HDF and its synthesis increased in stimulated cells, whereas IL-1Ra was present in low amounts in the supernatants. Secreted IL-1Ra (sIL-1Ra) and intracellular IL-1Ra type 1 (icIL-1Ra1) mRNA levels followed the same pattern.

Adipose tissue is a major source of interleukin-1 receptor antagonist: upregulation in obesity and inflammation.

The secreted form of the interleukin-1 receptor antagonist (IL-1Ra) is an acute-phase protein intervening in the counterregulation of inflammatory processes. We previously showed that this cytokine antagonist is upregulated in the serum of obese patients, correlating with BMI and insulin resistance. In this study, we examined the expression pattern of IL-1Ra and showed that it is highly expressed not only in liver and spleen, but also in white adipose tissue (WAT), where it is upregulated in obesity.

IP-10, but not RANTES, is upregulated by leptin in monocytic cells.

We and others have previously shown that leptin has direct effects on the function of monocytes and macrophages. Since obesity is associated with an increased cardiovascular risk, as well as with markedly elevated circulating leptin levels, we examined whether leptin has any pro-inflammatory effects on the function of monocytes. Leptin strongly enhanced the expression and secretion of the interferon-gamma-inducible protein (IP-10) in a human monocytic cell line, as well as in peripheral blood mononuclear cells.

Regulation of the interleukin-1 receptor antagonist in THP-1 cells by ligands of the peroxisome proliferator-activated receptor gamma.

Monocytes/macrophages (Mphi) play a pivotal role in the persistence of chronic inflammation and local tissue destruction in diseases such as rheumatoid arthritis and atherosclerosis. The production by Mphi of cytokines, chemokines, metalloproteinases and their inhibitors is an essential component in this process, which is tightly regulated by multiple factors. The peroxisome proliferator-activated receptors (PPARs) were shown to be involved in modulating inflammation.

Proinflammatory activity of TWEAK on human dermal fibroblasts and synoviocytes: blocking and enhancing effects of anti-TWEAK monoclonal antibodies.

Human tumour necrosis factor (TNF)-like weak inducer of apoptosis (hTWEAK) and two anti-hTWEAK mAbs were tested for their ability to elicit or block inflammatory responses in cultured human dermal fibroblasts and synoviocytes. Incubation with hTWEAK increased the production of prostaglandin E2, matrix metalloproteinase-1 (MMP-1), IL-6, and the chemokines IL-8, RANTES (regulated on activation, normal T expressed and secreted) and interferon-gamma-inducible protein-10 (IP-10) in culture supernatant of fibroblasts and synoviocytes. In combination with TNF or IL-1beta, hTWEAK further stimulated the secretion of prostaglandin E2, MMP-1, IL-6 and IL-8 up to fourfold, and IP-10 and RANTES up to 70-fold compared to TNF or IL-1beta alone.