Bone Morphogenic Proteins are Immunoregulatory Cytokines Controlling FOXP3+ T\u3csub\u3ereg\u3c/sub\u3e Cells

Bone morphogenic proteins (BMPs) are members of the transforming growth factor β (TGF-β) cytokine family promoting differentiation, homeostasis, and self-renewal of multiple tissues. We show that signaling through the bone morphogenic protein receptor 1α (BMPR1α) sustains expression of FOXP3 in Treg cells in peripheral lymphoid tissues. BMPR1α signaling promotes molecular circuits supporting acquisition and preservation of Treg cell phenotype and inhibiting differentiation of pro-inflammatory effector Th1/Th17 CD4+ T cell. Mechanistically, increased expression of KDM6B (JMJD3) histone demethylase, an antagonist of the polycomb repressive complex 2, underlies lineage-specific changes of T cell phenotypes associated with abrogation of BMPR1α signaling. These results reveal that BMPs are immunoregulatory cytokines mediating maturation and stability of peripheral FOXP3+ regulatory T cells (Treg cells) and controlling generation of iTreg cells. Thus, we establish that BMPs, a large cytokine family, are an essential link between stromal tissues and the adaptive immune system involved in sustaining tissue homeostasis by promoting immunological tolerance

Thymus-derived regulatory T cells control tolerance to commensal microbiota

Peripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4+Foxp3+ regulatory T cells1,2 generated in the thymus (tTregs) or extrathymically by induction of naive CD4+Foxp3− T cells (iTregs). Prior studies suggested that the T cell receptor (TCR) repertoires of tTregs and iTregs are biased towards self and non-self antigens, respectively 3–6 but their relative contribution in controlling immunopathology, e.g. colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved 7. The intestine, and especially the colon, is a particularly suitable organ to study this question, given the variety of self-, microbiota- and food-derived antigens to which Tregs and other T cell populations are exposed. Intestinal environments can enhance conversion to a regulatory lineage 8,9 and favor tolerogenic presentation of antigens to naive CD4+ T cells 10,11, suggesting that intestinal homeostasis depends on microbiota-specific iTregs 12–15. Here, to identify the origin and antigen-specificity of intestinal Tregs, we performed single cell as well as high-throughput (HT) sequencing of the TCR repertoires of CD4+Foxp3+ and CD4+Foxp3− T cells and analyzed their reactivity against specific commensal species. We show that tTregs constitute the majority of Tregs in all lymphoid and intestinal organs, including colon, where their repertoire is heavily influenced by the composition of the microbiota. Our results suggest that tTregs, and not iTregs, dominantly mediate tolerance to antigens produced by intestinal commensals

Higher-Order VLP-Based Protein Macromolecular Framework Structures Assembled via Coiled-Coil Interactions

Hierarchical organization is one of the fundamental features observed in biological systems that allows for efficient and effective functioning. Virus-like particles (VLPs) are elegant examples of a hierarchically organized supramolecular structure, where many subunits are self-assembled to generate the functional cage-like architecture. Utilizing VLPs as building blocks to construct two- and three-dimensional (3D) higher-order structures is an emerging research area in developing functional biomimetic materials. VLPs derived from P22 bacteriophages can be repurposed as nanoreactors by encapsulating enzymes and modular units to build higher-order catalytic materials via several techniques. In this study, we have used coiled-coil peptide interactions to mediate the P22 interparticle assembly into a highly stable, amorphous protein macromolecular framework (PMF) material, where the assembly does not depend on the VLP morphology, a limitation observed in previously reported P22 PMF assemblies. Many encapsulated enzymes lose their optimum functionalities under the harsh conditions that are required for the P22 VLP morphology transitions. Therefore, the coiled-coil-based PMF provides a fitting and versatile platform for constructing functional higher-order catalytic materials compatible with sensitive enzymes. We have characterized the material properties of the PMF and utilized the disordered PMF to construct a biocatalytic 3D material performing single- and multistep catalysis

Iron Oxide and Titanium Dioxide Nanoparticle Effects on Plant Performance and Root Associated Microbes

In this study, we investigated the effect of positively and negatively charged Fe3O4 and TiO2 nanoparticles (NPs) on the growth of soybean plants (Glycine max.) and their root associated soil microbes. Soybean plants were grown in a greenhouse for six weeks after application of different amounts of NPs, and plant growth and nutrient content were examined. Roots were analyzed for colonization by arbuscular mycorrhizal (AM) fungi and nodule-forming nitrogen fixing bacteria using DNA-based techniques. We found that plant growth was significantly lower with the application of TiO2 as compared to Fe3O4 NPs. The leaf carbon was also marginally significant lower in plants treated with TiO2 NPs; however, leaf phosphorus was reduced in plants treated with Fe3O4. We found no effects of NP type, concentration, or charge on the community structure of either rhizobia or AM fungi colonizing plant roots. However, the charge of the Fe3O4 NPs affected both colonization of the root system by rhizobia as well as leaf phosphorus content. Our results indicate that the type of NP can affect plant growth and nutrient content in an agriculturally important crop species, and that the charge of these particles influences the colonization of the root system by nitrogen-fixing bacteria