Biology subjects

Rowe, R. K.

Publications and source records attributed to Rowe, R. K..

6 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

FcϵRI+IgE+ monocytes are linked to atopy and allergic inflammation with distinct phenotypes and enhanced antiviral responses

Monocytes are critical regulators of allergic inflammation, whose functions are modified by IgE-driven processes. Monocytes are heterogeneous; comprised of multiple subsets which implies differential functions. In allergic inflammation, this heterogeneity is likely influenced by IgE-mediated effects. We sought to identify phenotypically distinct monocyte subsets related to allergic disease and then further delineate functional differences in cytokine release and antiviral responses. Using high dimensional spectral flow cytometry, we identified monocyte surface phenotypes directly related to surface levels of the high affinity IgE receptor (Fc{varepsilon}RI) and surface-bound IgE. Fc{varepsilon}RI+IgE+ monocytes, or FIMs, correlated with allergic disease and the level of atopy (i.e. serum IgE levels) of individual subjects. The FIM population also had differential surface expression of other molecules of monocyte maturation, which closely resembled a type 2 conventional dendritic cell (cDC2) phenotype. Functionally, FIMs had enhanced antiviral responses and IgE-driven IL-10 cytokine release. Finally, we showed that FIMs could be identified at higher levels in lung tissue from individuals with asthma. This study supports that atopic disease drives differential monocyte phenotypes, with the FIM population, specifically, as a more mature cell population closely related to dendritic cells with enhanced antiviral responses. The presence of monocytes in lung tissue during lethal asthma exacerbation further supports a role in regulating tissue inflammatory responses in allergic airway disease.

immunology↗

bioRxiv2026

Transcriptional regulation of the main olfactory epithelium by environmental olfactory exposures

The nasal epithelium is a complex tissue composed of both respiratory and olfactory tissue, and is constantly exposed to environmental insults, including toxins and pathogens. The main olfactory epithelium (MOE) serves as the critical site for olfaction, or sense of smell. Dysfunction at this critical barrier tissue can result in partial or total loss of olfactory function, resulting in significant impact to quality of life. The MOE is heterogeneous, comprised of many cell types including olfactory sensory neurons, support cells, and immune cells. It is not well understood how these diverse cell types in the MOE interact to regulate this tissue during homeostasis, and during times of injury and inflammation. We investigated how environmental olfactory exposures impact cell type specific transcriptional responses in the mouse MOE. We performed single-cell RNA sequencing (scRNA-seq) of the MOE following controlled environmental exposure to both well-known odorants and allergens. We identified major cell types and subtypes within the MOE, and identified transcriptional changes in response to the olfactory exposures. We identified transcriptional changes in OSNs, sustentacular cells, and resident immune cells to each condition. This indicated that environmental olfactory exposures drive changes to multiple cell types in the MOE. To our knowledge, this is the first study to identify effects of environmental olfactory exposures on cell-type specific transcription at homeostasis. These findings highlight the potential importance of multi-cellular interactions and communication in regulation of the olfactory epithelium.

neuroscience↗

bioRxiv2024

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↗

bioRxiv2020

Spatial distribution of neuropathology and neuroinflammation elucidate the biomechanics of fluid percussion injury

Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. Finite element biomechanical models of diffuse brain injury predict regions of maximum stress and strain. However, the application of a skull with uniform thickness may mask the pathophysiology due to varying thickness of human and animal skulls. Force applied to the intact skull would diffuse the forces, whereas forces applied through an open skull are distributed along paths of least resistance within and then exiting the skull. We hypothesized that the local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology in underlying cortical tissue. We demonstrated local thickening of the skull at the temporal ridges using contour analysis of coronal skull sections and oblique sectioning on MRI. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge due to the material properties of the skull based on thickness, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge prior to injury reduced the injury-induced inflammation in sensorimotor cortex. These data build evidence for the temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy. HighlightsO_LIThe temporal ridge is 75% thicker than the adjacent skull of the rodent C_LIO_LIExperimental diffuse TBI neuropathology occurs beneath the length of the temporal ridge C_LIO_LINeuropathology encompasses sensorimotor cortex, somatosensory thalamus, and dorsolateral hippocampus C_LIO_LIProposed mechanism of biomechanical injury forces include the temporal ridge C_LI

neuroscience↗

bioRxiv2018

Type I Interferon regulates IgE-mediated enhancement of rhinovirus-induced Th2 priming by primary human monocytes

Rhinovirus infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate dendritic cell antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 priming. In this study, we investigate the effects of IgE-mediated allergic stimulation on monocyte-driven, RV-induced T cell priming utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 priming. This increase in RV-induced Th2 differentiation was regulated by IgE-mediated inhibition of type I interferon and induction of IL-10. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations - IgE-mediated stimulation and rhinovirus infection, may synergistically promote Th2 differentiation and allergic inflammation.

immunology↗