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The IL-4 receptor: signaling mechanisms and biologic functions.

TLDR
The modular nature of the IL-4 receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation are emphasized.
Abstract
▪ Abstract Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4Rα chain and the common gamma chain (γc), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.

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Journal ArticleDOI

Alternative activation of macrophages

TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Journal ArticleDOI

A novel transcription factor, T-bet, directs Th1 lineage commitment.

TL;DR: T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs, as evidenced by the simultaneous induction of IFNgamma and repression of IL-4 and IL-5.
Journal ArticleDOI

Recognition of microorganisms and activation of the immune response.

TL;DR: The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections, and recent progress brings us closer to an integrated view of the immune system and its function in host defence.
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Alternative Activation of Macrophages: An Immunologic Functional Perspective

TL;DR: The cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures are reviewed and the concept of macrophage activation in the context of the immune response is revisit.
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Follicular Helper CD4 T Cells (TFH)

TL;DR: This review discusses recent progress and areas of uncertainty or disagreement in the literature, and debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).
References
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Journal ArticleDOI

STATs and Gene Regulation

TL;DR: The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.
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Protein modules and signalling networks

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
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Human Growth Hormone and Extracellular Domain of Its Receptor: Crystal Structure of the Complex

TL;DR: Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor.
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A family of cytokine-inducible inhibitors of signalling

TL;DR: Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction.
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