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Matthews, B. E.

Publications and source records attributed to Matthews, B. E..

2 recordsLinked to original sources

Effects of acute intranasal allergen exposure on resident immune cells and sensory neurons in the mouse olfactory epithelium

The main olfactory epithelium (MOE) is the primary site of olfaction and consists of multiple cell types including olfactory sensory neurons (OSNs), sustentacular cells, and immune cells. Neuroimmune interactions in epithelial tissues are critical in maintaining tissue function, but how OSNs and immune cells interact in the MOE in healthy and diseased states is largely unknown. Cellular responses in the MOE determine how and whether OSNs maintain olfactory function and are repaired or replenished following inflammatory environmental exposures. We hypothesized that acute nasal aeroallergen exposure alters immune cell function in the MOE to elicit a neuroprotective response, thereby preserving OSN function. We developed an environmental aeroallergen exposure consisting of one week of daily intranasal house dust mite extract (HDM) instillations. Spectral flow cytometry indicated only subtle changes in resident immune cells proportions and phenotypes in the MOE. Immunohistochemical evaluation did not reveal extensive changes in immune cell distribution in the sensory epithelium or lamina propria, but instead we observed increases in axonal olfactory marker protein (OMP) expression in the lamina propria, where resident immune cells are most abundant. To evaluate the effects of HDM exposure on OSN function, we performed live ex vivo Ca2+ imaging of MOEs from HDM- and sham-exposed transgenic mice using objective-coupled planar illumination (OCPI) microscopy. OSN responses to multiple odorants revealed increased chemosensory sensitivity and decreased across-trial adaptation in HDM-treated epithelia. These results indicate that short-term nasal aeroallergen exposure minimally alters immune cell phenotypes, and instead induces functional changes in OSN physiology that preserve olfactory function.

neuroscience↗

SHIP-1 differentially regulates IgE-induced IL-10 and antiviral responses in human monocytes

IgE-mediated stimulation of monocytes regulates multiple cellular functions including cellular maturation, cytokine release, antiviral responses, and T cell priming and differentiation. The high affinity IgE receptor, Fc{varepsilon}RI, is closely linked to serum IgE levels and atopic disease. The signaling molecules which regulate effector functions of this receptor have been well studied in mast cells and basophils, however, less is known about the signaling components, regulatory molecules, and mechanisms downstream of receptor activation in monocytes. This study sought to identify regulators of IgE-mediated cytokine release in human monocytes. SHIP-1 was identified as a negative regulator of IgE-induced IL-10 production. It was also determined that IgE-mediated stimulation and SHIP-1 inhibition decreased antiviral IP-10 production after liposomal poly(I:C) stimulation, indicating differential regulation by SHIP-1 in IgE-driven and antiviral response pathways. Both SHIP-1 and NF-{kappa}B were activated following IgE-mediated stimulation of primary monocytes, and NF-{kappa}B activation was related to both SHIP-1 and Fc{varepsilon}RI expression levels in monocytes. To our knowledge this is the first study to identify a role for SHIP-1 in regulating IgE-driven responses and antiviral responses in human monocytes. Given the importance of monocytes in inflammation and immune responses, a better understanding of the signaling and regulatory mechanisms downstream of Fc{varepsilon}RI receptor could lead to new therapeutic targets in allergic disease.

immunology↗