A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor α determines T cell activation and function.

Ligation of retinoic acid receptor alpha (RARα) by RA promotes varied transcriptional programs associated with immune activation and tolerance, but genetic deletion approaches suggest the impact of RARα on TCR signaling. Here, we examined whether RARα would exert roles beyond transcriptional regulation. Specific deletion of the nuclear isoform of RARα revealed an RARα isoform in the cytoplasm of T cells.

Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System.

Vitamin A is a multifunctional vitamin implicated in a wide range of biological processes. Its control over the immune system and functions are perhaps the most pleiotropic not only for development but also for the functional fate of almost every cell involved in protective or regulatory adaptive or innate immunity. This is especially key at the intestinal border, where dietary vitamin A is first absorbed.

FoxO3 is a negative regulator of primary CD8+ T-cell expansion but not of memory formation.

The generation of CD8(+) T cells by vaccination represents an important goal for protective immunity to infectious pathogens. It is thus of utmost importance to understand the mechanisms involved in the generation of optimal CD8(+) T-cell responses. The forkhead box O (FoxO) family of transcription factors has a crucial role in cellular responses to environmental change.

HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria.

The herpes virus entry mediator (HVEM), a member of the tumour-necrosis factor receptor family, has diverse functions, augmenting or inhibiting the immune response. HVEM was recently reported as a colitis risk locus in patients, and in a mouse model of colitis we demonstrated an anti-inflammatory role for HVEM, but its mechanism of action in the mucosal immune system was unknown. Here we report an important role for epithelial HVEM in innate mucosal defence against pathogenic bacteria.

Glucocorticoids inhibit dendritic cell maturation induced by Toll-like receptor 7 and Toll-like receptor 8.

GCs are widely prescribed to treat inflammatory disorders and autoimmune and allergic diseases. Their anti-inflammatory and immunosuppressive effects may be related, in part, to their ability to control the maturation and functions of DCs. Here, we report that GCs inhibit the maturation of human CD34-DCs induced by the TLR7 agonist imiquimod and the TLR8 agonist 3M-002.

Mucosal memory CD8⁺ T cells are selected in the periphery by an MHC class I molecule.

The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8αα on activated CD8αβ(+) T cells, mediated affinity-based selection of memory precursor cells.

Mechanisms of IL-12 synthesis by human dendritic cells treated with the chemical sensitizer NiSO4.

Allergic contact dermatitis, caused by metallic ions, is a T cell-mediated inflammatory skin disease. IL-12 is a 70-kDa heterodimeric protein composed of IL-12p40 and IL-12p35, playing a major role in the generation of allergen-specific T cell responses. Dendritic cells (DCs) are APCs involved in the induction of primary immune responses, as they possess the ability to stimulate naive T cells.

TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation.

Dendritic cells (DCs) play an important role in bridging innate and adaptive immunity. These APCs have the ability to recognize specific molecular signatures of pathogens through TLRs. In particular, the intracellular TLR7 and TLR8, mediating the recognition of ssRNA by DCs, play a major role in the immune response during viral infection.

Metallic haptens induce differential phenotype of human dendritic cells through activation of mitogen-activated protein kinase and NF-kappaB pathways.

Dendritic cells (DCs) play a major role in the regulation of immune responses to a variety of antigens (Ag) and haptens which participate in the process of DC maturation. Indeed, metallic haptens are able to induce DC maturation in vitro but the mechanism of this maturation is not well understood. We and others have already shown that NiSO(4) activates p38 mitogen-activated protein kinases (p38MAPK), c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and the transcription factor NF-kappaB during the early events of DCs maturation.