Mutual Interaction of Basophils and T Cells in Chronic Inflammatory Diseases

Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high affinity receptor for IgE (FcεR1), release histamine, inflammatory mediators and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid and non-lymphoid tissues and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2 and Th17 cells, as well as their potential role in IgE-independent non allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases

SUPPRESSOR T LYMPHOCYTES IN PREGNANCY

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The blurred boundaries of ecological, sustainable, and agroecological intensification: a review

International audienceAbstractThe projected human population of nine billion by 2050 has led to ever growing discussion of the need for increasing agricultural output to meet estimated food demands, while mitigating environmental costs. Many stakeholders in agricultural circles are calling for the intensification of agriculture to meet these demands. However, it is neither clear nor readily agreed upon what is meant by intensification. Here, we compare the three major uses, ‘ecological intensification’, ‘sustainable intensification’ and ‘agroecological intensification’, by analysing their various definitions, principles and practices, and also their historical appearance and evolution. We used data from the scientific literature, the grey literature, the websites of international organizations and the Scopus and FAOLEX databases. Our major findings are: (1) sustainable intensification is the most frequently used term so far. (2) The three concepts ecological intensification, sustainable intensification and agroecological intensification overlap in terms of definitions, principles and practices, thus creating some confusion in their meanings, interpretations and implications. Nevertheless, some differences exist. (3) Sustainable intensification is more widely used and represents in many cases a rather generalised category, into which most current farming practices can be put so long as sustainability is in some way addressed. However, despite its wider use, it remains imprecisely defined. (4) Ecological and agroecological intensification do introduce some major nuances and, in general, more explicitly stated definitions. For instance, ecological intensification emphasizes the understanding and intensification of biological and ecological processes and functions in agroecosystem. (5) The notion of agroecological intensification accentuates the system approach and integrates more cultural and social perspectives in its concept. (6) Even if some boundaries can be seen, confusion is still predominant in the use of these terms. These blurred boundaries currently contribute to the use of these terms for justifying many different kinds of practices and interventions. We suggest that greater precision in defining the terms and the respective practices proposed would indicate more clearly what authors or institutions are aiming at with the proposed intensification. In this sense, we provide new definitions for all three intensification concepts based on the earlier ones

The role of PKCzeta in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil

While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.Hani Harb, James Irvine, Manori Amarasekera, Charles S. Hii, Dörthe A. Kesper, YueFang Ma, Nina D′Vaz, Harald Renz, Daniel P. Potaczek, Susan L. Prescott and Antonio Ferrant

Thrombospondin 1 Is an Autocrine Negative Regulator of Human Dendritic Cell Activation

Thrombospondin 1 (TSP) elicits potent antiinflammatory activities in vivo, as evidenced by persistent, multiorgan inflammation in TSP null mice. Herein, we report that DCs represent an abundant source of TSP at steady state and during activation. Human monocyte-derived immature dendritic cells (iDCs) spontaneously produce TSP, which is strongly enhanced by PGE2 and to a lesser extent by transforming growth factor (TGF) β, two soluble mediators secreted by macrophages after engulfment of damaged tissues. Shortly after activation via danger signals, DCs transiently produce interleukin (IL) 12 and tumor necrosis factor (TNF) α, thereby eliciting protective and inflammatory immune responses. Microbial stimuli increase TSP production, which is further enhanced by IL-10 or TGF-β. The endogenous TSP produced during early DC activation negatively regulates IL-12, TNF-α, and IL-10 release through its interactions with CD47 and CD36. After prolonged activation, DCs extinguish their cytokine synthesis and become refractory to subsequent stimulation, thereby favoring the return to steady state. Such “exhausted” DCs continue to release TSP but not IL-10. Disrupting TSP–CD47 interactions during their restimulation restores their cytokine production. We conclude that DC-derived TSP serves as a previously unappreciated negative regulator contributing to arrest of cytokine production, further supporting its fundamental role in vivo in the active resolution of inflammation and maintenance of steady state