Sterility testing of germ-free mouse colonies.

In biomedical research, germ-free and gnotobiotic mouse models enable the mechanistic investigation of microbiota-host interactions and their role on (patho)physiology. Throughout any gnotobiotic experiment, standardized and periodic microbiological testing of defined gnotobiotic housing conditions is a key requirement. Here, we review basic principles of germ-free isolator technology, the suitability of various sterilization methods, and the use of sterility testing methods to monitor germ-free mouse colonies.

IL-27 Enhances γδ T Cell-Mediated Innate Resistance to Primary Hookworm Infection in the Lungs.

IL-27 is a heterodimeric IL-12 family cytokine formed by noncovalent association of the promiscuous EBI3 subunit and selective p28 subunit. IL-27 is produced by mononuclear phagocytes and unfolds pleiotropic immune-modulatory functions through ligation to IL-27 receptor α (IL-27RA). Although IL-27 is known to contribute to immunity and to limit inflammation after various infections, its relevance for host defense against multicellular parasites is still poorly defined.

microRNA-92a promotes CNS autoimmunity by modulating the regulatory and inflammatory T cell balance.

A disequilibrium between immunosuppressive Tregs and inflammatory IL-17-producing Th17 cells is a hallmark of autoimmune diseases, including multiple sclerosis (MS). However, the molecular mechanisms underlying the Treg and Th17 imbalance in CNS autoimmunity remain largely unclear. Identifying the factors that drive this imbalance is of high clinical interest.

MicroRNA-146a limits tumorigenic inflammation in colorectal cancer.

Chronic inflammation can drive tumor development. Here, we have identified microRNA-146a (miR-146a) as a major negative regulator of colonic inflammation and associated tumorigenesis by modulating IL-17 responses. MiR-146a-deficient mice are susceptible to both colitis-associated and sporadic colorectal cancer (CRC), presenting with enhanced tumorigenic IL-17 signaling.

PD1 Blockade in Cancer: Impact on Myeloid Cells.

Programmed death 1 (PD1) has emerged as a major inhibitor of antitumor T cells, and anti-PD1 therapies have demonstrated clinical efficacy in multiple cancers. However, the impact of PD1 on other immune cells had remained unclear. A recent study by Strauss et al.

Remyelination-Promoting Inflammation: Novel Role for MyD88 Signaling in Microglia/Macrophages.

Inflammation in the central nervous system (CNS) has been linked to demyelination and remyelination. Using zebrafish and mouse models of demyelination and remyelination, Cunha et al. now describe a novel role for myeloid differentiation factor 88 (MyD88) signaling in supporting remyelination by promoting myeloid cell-mediated inflammatory responses via TNF-α, which are essential for phagocytic myelin debris clearance and for oligodendrogenesis.

Smad7 Controls Immunoregulatory PDL2/1-PD1 Signaling in Intestinal Inflammation and Autoimmunity.

Smad7, a negative regulator of TGF-β signaling, has been implicated in the pathogenesis and treatment of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC). Here, we found that Smad7 mediates intestinal inflammation by limiting the PDL2/1-PD1 axis in dendritic cells (DCs) and CD4T cells. Smad7 deficiency in DCs promotes TGF-β responsiveness and the co-inhibitory molecules PDL2/1 on DCs, and it further imprints T cell-PD1 signaling to promote Treg differentiation.

Flow Cytometric Assessment of STAT Molecules in Th9 Cells.

IL-9-producing Th9 cells are a novel subset of T helper cells that develop independently of other T helper subsets. Th9 cells have been implicated in the pathogenesis of allergic asthma and autoimmunity, while also serving as critical effector T cells in mediating antitumor immune responses. Concomitant presence of TGF-β and IL-4 lead to the differentiation of naïve CD4 T cells towards the Th9 phenotype.

Contribution of MicroRNAs to autoimmune diseases.

MicroRNAs are a class of evolutionarily conserved, short non-coding RNAs that post-transcriptionally modulate the expression of multiple target genes. They are implicated in almost every biological process, including pathways involved in immune homeostasis, such as immune cell development, central and peripheral tolerance, and T helper cell differentiation. Alterations in miRNA expression and function can lead to major dysfunction of the immune system and mediate susceptibility to autoimmune disease.

The Use of MiRNA Antagonists in the Alleviation of Inflammatory Disorders.

Toll-like receptors (TLR), a family of pattern-recognition receptors (PRRs) stimulated by pathogen-associated molecular patterns (PAMPs), generate antigen-triggered innate and adaptive immune responses. Recent studies have indicated that several small, regulatory RNAs, called microRNAs (miRNas), are induced by TLR activation in immune cells and that many microRNAs can control the inflammatory process and response to infection by positively or negatively regulating TLR signaling. Among these miRNAs, aberrant microRNA-155 (miR-155) has been implicated in diverse immune processes including the pathogenesis of several autoimmune diseases and cancer.

Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.

Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans.

MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis.

Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimmune diseases; however, the contribution of microRNA (miRNA) pathways to the intrinsic control of Th17 development remains unclear. Here, we demonstrated that miR-21 expression is elevated in Th17 cells and that mice lacking miR-21 have a defect in Th17 differentiation and are resistant to experimental autoimmune encephalomyelitis (EAE). Furthermore, we determined that miR-21 promotes Th17 differentiation by targeting and depleting SMAD-7, a negative regulator of TGF-β signaling.