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Defective tissue repair is a hallmark of many inflammatory disorders including, inflammatory bowel disease (IBD). While it is clear that high fat diets (HFD) can exacerbate inflammatory disease by increasing inflammation, the direct effect of lipids on tissue homeostasis and repair remains undefined. We show here that short term exposure to HFD directly impairs barrier repair after intestinal epithelial damage by interfering with recognition and uptake of apoptotic neutrophils by intestinal macrophages. Apoptotic neutrophil uptake induces macrophage IL-10 production, which is lacking after intestinal damage in the context of HFD. Overexpression of IL-10 rescues repair defects after HFD treatment, but not if epithelial cells lack the IL-10 receptor, highlighting the key role of IL-10 in barrier repair. These findings demonstrate a previously unidentified mechanism by which dietary lipids directly interfere with homeostatic processes required to maintain tissue integrity.

It is known that the gut commensal bacteria support intestinal epithelial barrier integrity. However, how specific microbes regulate barrier integrity is not fully understood. We and others find that barrier repair in models of colitis requires the microbiota and asked whether individual microbes are sufficient to replace functions of the total microbiota. We identified a mouse commensal E. coli that protects mice from enhanced damage in the absence of the microbiota in a mouse model of infectious colitis. Surprisingly, the protective E. coli induced IL-1β production by intestinal macrophages in vivo. Such IL-1β secretion activated type 3 innate lymphoid cells (ILC3) and induced IL-22 production that triggered epithelial barrier repair. In addition to mouse commensal E. coli, we also identified a subset of human E. coli isolates that offered protection utilizing the same cellular and molecular pathways. Together, we reveal a novel mechanism that select intestinal commensal bacteria activate inflammatory pathways to support gut barrier repair and maintain barrier integrity.

Here, we report the size- and shape-controlled synthesis of metal oxide nanoparticles through the introduction of rare-earth metals. The addition of gadolinium oleate in the synthesis of iron oxide nanoparticles induced sphere-to-cube shape changes of nanoparticles and generated iron oxide nanocubes coated with gadolinium. Based on experimental investigations and density functional theory (DFT) calculations, we attribute the shape change to the facet-selective binding of undecomposed gadolinium oleates. While many previous studies on the shape-controlled syntheses of nanoparticles rely on the stabilization of specific crystal facets by anionic surfactants or their decomposition products, this study shows that the interaction between growing transition metal oxide nanoparticles and rare-earth metal complexes can be used as a robust new mechanism for shape-controlled syntheses. Indeed, we demonstrated that this approach was applicable to other transition metal oxide nanoparticles (i.e., manganese oxide and manganese ferrite) and rare earth metals (i.e., gadolinium, europium, and cerium). This study also demonstrates that the nature of metal-ligand bonding can play an important role in the shape control of nanoparticles.

The intestinal epithelial barrier critically separates exogenous microbes from our internal tissues. Signals from commensal microbes are known to support intestinal barrier integrity and repair. However, the role of specific microbes in maintaining the intestinal barrier is not well-defined. We hypothesize that signals from distinct commensal microbes play different roles in regulating the barrier. We find that mice develop severe colitis with decreased ability to repair the intestinal barrier after antibiotic depletion of intestinal microbes. We further isolated a mouse commensal E. coli that protects from increased colitis after antibiotic treatment. This protection depends on the presence of intestinal antigen presenting cells (APCs) that express the chemokine receptor CX3CR1. We screened a panel of human mucosal-associated E. coli and identified a subset that also protect from colitis in a CX3CR1+ APC dependent manner. All protective E. coli induce IL-1β secretion by activation of the non-canonical inflammasome pathway in CX3CR1+ APCs. In vivo protection is lost if IL-1β signaling is blocked with anti-IL-1β antibody. This E. coli induced IL-1β production activates type 3 innate lymphoid cells (ILC3) to produce IL-22 which drives epithelial proliferation and barrier repair. Collectively, we identified a novel mechanism by which a subset of mucosal-associated intestinal E. coli activate IL-1β production by APCs to protect the intestinal barrier from damage.

Epidemiological evidence finds cigarette smoking is a common risk factor for a number of diseases, not only in the lung but also in other tissues, such as the gastrointestinal tract. While it is well-documented that smoking directly drives lung inflammatory disease, how it promotes disease in peripheral tissues is incompletely understood. In this study, we utilized a mouse model of short-term smoke exposure and found increased Th17 cells and neutrophilia in the lung as well as in the circulation. Following intestinal inflammatory challenge, smoke exposed mice showed increased pathology which corresponds to enhanced intestinal Th17 cells, ILC3 and neutrophils within intestinal tissue. Using cellular depletion and genetic deficiencies, we define a cellular loop by which IL-17A and downstream neutrophils drive cigarette smoke-enhanced intestinal inflammation. Collectively, cigarette smoke induced local lung Th17 responses lead to increased systemic susceptibility to inflammatory insult through enhanced circulating neutrophils. These data demonstrate a cellular pathway by which inflammatory challenge in the lung can sensitize the intestine to enhanced pathological innate and adaptive immune responses.

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.

Efficient functioning of the intestine and intestinal immune system depends on interactions between the host and microbiota. Breakdown in these interactions leads to reduced ability to respond to intestinal pathogens along with increased intestinal inflammation which together can lead to pathologic inflammatory conditions such as inflammatory bowel disease. While a number of intestinal immune cells are likely regulated by the microbiota, we have found critical regulation of intestinal antigen presenting cells (APCs) expressing the chemokine receptor, CX3CR1. CX3CR1+ APCs are able to secrete both pro- and anti-inflammatory cytokines and are capable of mediating intestinal protection or pathology. Using in vivo models, we identified a regulatory loop whereby intestinal CX3CR1+ APCs reduced induction of Th1 cells against intestinal pathogens and promoted generation of regulatory T cells against soluble food antigens and the microbiota itself. This regulatory response depends on anti-inflammatory cytokine IL-10 production by CX3CR1+ APCs. Disruption of the intestinal microbiota switched the functional capacity of CX3CR1+ APCs so they now drove inflammatory Th1 responses and mediated pathology in a model of colitis. Mechanistically, we determined that epithelial attachment by intestinal microbes was required to turn on anti-inflammatory functions by CX3CR1+ APCs. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes homeostasis. Our study demonstrates the potential therapeutic benefits of microbiota and host immune cell manipulation with the goal of amplifying or inhibiting intestinal T cell responses.

We have proposed a novel ultra wideband monopole antenna using parasitic open loops for UWB applications. The proposed antenna consists of a center monopole, two symmetrical open loops, and CPW feeding. The combining technique of orthogonal electric and magnetic dipoles is used to design the proposed antenna. Symmetrical structure is the key concept for achieving an ultra wideband impedance matching and very low dispersion over the operating frequency band (3.1 ∼ 4.8 GHz). The group delay was measured as a function of the azimuth angle φ. The radiation patterns are very close to those of a conventional dipole antenna and the simulated antenna gain varies from 2 dBi to 3.2 dBi over the operating frequency range.