Biology subjects

Farrar, J. D.

Publications and source records attributed to Farrar, J. D..

3 recordsLinked to original sources

bioRxiv2024

Differences in systemic immune parameters in individuals with lung cancer according to race

IntroductionRacial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer. MethodsPatients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pre-treatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons. ResultsA total of 187 patients with non-small cell lung cancer (Black, 19; White, 168) were included in the analysis. There were no significant differences in baseline characteristics between Black and White patients. Compared to White patients, Black patients had significantly lower levels of CCL23 and CCL27, and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1 b, CXCL16, and IFN-{gamma} (all P<0.05, FDR<0.1). Black patients also exhibited greater populations of non-classical CD16+ monocytes, NKT-like cells, CD4+ cells, CD38+ monocytes, and CD57+ gamma delta T cells (all P<0.05). ConclusionsBlack and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous pro-inflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.

cancer biology↗

bioRxiv2024

The β2-adrenergic receptor (ADRB2) entrains circadian gene oscillation and diurnal responses to virus infection in CD8+ T cells

Adaptive immune cells are regulated by circadian rhythms (CR) under both steady state conditions and during responses to infection. Cytolytic CD8+ T cells display variable responses to infection depending upon the time of day of exposure. However, the neuronal signals that entrain these cyclic behaviors remain unknown. Immune cells express a variety of neurotransmitter receptors including nicotinic, glucocorticoid, and adrenergic receptors. Here, we demonstrate that the {beta}2-adrenergic receptor (ADRB2) regulates the periodic oscillation of select core clock genes, such as Per2 and Bmal1, and selective loss of the Adrb2 gene dramatically perturbs the normal diurnal oscillation of clock gene expression in CD8+ T cells. Consequently, their circadian-regulated anti-viral response is dysregulated, and the diurnal development of CD8+ T cells into variegated populations of cytolytic T cell (CTL) effectors is dramatically altered in the absence of ADRB2 signaling. Thus, the Adrb2 directly entrains core clock gene oscillation and regulates CR-dependent T cell responses to virus infection as a function of time-of-day of pathogen exposure. One Sentence SummaryThe {beta}2-adrenergic receptor regulates circadian gene oscillation and downstream daily timing of cytolytic T cell responses to virus infection.

immunology↗

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↗