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Cellular caspase-8 (FLICE)-like inhibitory protein (cFLIP) was originally identified as an inhibitor of death-receptor signalling. However, this Review discusses new data indicating that cFLIP is also required for the survival and proliferation of T cells following T-cell-receptor stimulation.
In this Opinion article, the authors propose that liver disease occurring in patients with inflammatory bowel disease is mediated by aberrant homing of gut-derived T cells to the liver, owing to abnormal expression of chemokines and adhesion molecules.
The authors of this article describe the role of tertiary lymphoid organs in sustaining chronic inflammatory disease and compare the induction and function of such lymphoid neogenesis with that of conventional secondary lymphoid organs.
The CATERPILLER family of proteins, like the mammalian Toll-like receptors, are sensors of microbial products and regulators of the immune reponse. Genetic defects in CATERPILLER genes are associated with various immunological disorders, including hereditary periodic fevers, indicating that CATERPILLERs are important in regulating inflammatory responses.
This article provides an overview of the mechanisms by which eukaryotic cells sense and respond to chromosomal double-stranded DNA breaks and describes the importance of this response for the development of lymphocytes and the development of effective innate and adaptive immune responses.
This article aims to educate immunologists about the key role of neutrophils in the initiation of immune responses, and it describes how, in contrast to conventional wisdom, neutrophils mount responses specific to their environment, making them potential targets to treat inflammation.
Mast-cell activation is a key event in allergic reactions and largely results from signalling through the high-affinity receptor for IgE. However, complementary signalling pathways might also influence mast-cell-mediator release and might be activated by other receptors, such as KIT.
Recent data indicate that chemokines have a role in regulating dendritic-cell maturation. In this Opinion article it is proposed that this ensures that dendritic cells migrating to the lymph node arrive in a fully mature state that is optimal for T-cell priming.
Mucosal immunization could be our best hope for protection against pathogens that infect mucosal tissues. Here, the authors describe how our accumulating knowledge of the mechanisms of mucosal immune defence is being applied to mucosal vaccine design, in particular against HIV.
As thymocytes travel through the thymus, they not only receive signals from stromal cells but also deliver signals to stromal cells to generate the appropriate stromal environment. Takahama describes the factors involved in this lympho–stromal crosstalk for thymocyte trafficking and T-cell-repertoire selection.
All cells of the immune system are derived from precursor cells in the bone marrow known as haematopoietic stem cells (HSCs). This Review describes recent advances in our understanding of the specialized bone-marrow niches that regulate HSC differentiation and self-renewal.
Recent studies have identified potential factors and cellular environments that foster B-cell development in the bone marrow. As discussed, knowledge of such microenvironmental niches and of B-cell precursor populations has advanced our understanding of the spatiotemporal regulation of B-cell development.
Although T cells are derived from haematopoietic stem cells in the bone marrow, T-cell development occurs in the thymus. This Review describes recent data indicating that several cell populations in the bone marrow are able to populate the thymus and generate T cells.
Different pathogens have evolved distinct strategies to promote their survival in host cells. This Review describes the contribution of the endoplasmic reticulum to host defence and the mechanisms by which pathogens interacting with the endoplasmic reticulum subvert the host immune response.
This article describes the recent studies that elucidate the mechanism of action of the adaptor proteins SLP76 and SLP65. It details their crucial role in signalling by immunoreceptors and integrins, as well as their further unexpected roles in vascular development and leukaemia.
In this Opinion article, Thomas Boehm proposes that quality-control mechanisms, such as the MHC peptide-presentation system, that tame immunoreceptor self-reactivity might be derived from an ancestral mechanism that guided sexual selection and similarly used information contained in intracellular peptide sequences.
Members of the signalling lymphocytic activation molecule (SLAM) family of receptors associate with adaptor molecules of the SLAM-associated protein (SAP) family and have an important role in various aspects of innate and adaptive immune responses.
