sLeX Expression Delineates Distinct Functional Subsets of Human Blood Central and Effector Memory T Cells.

Sialyl Lewis X (sLeX) regulates T cell trafficking from the vasculature into skin and sites of inflammation, thereby playing a critical role in immunity. In healthy persons, only a small proportion of human blood T cells express sLeX, and their function is not fully defined. Using a combination of biochemical and functional studies, we find that human blood sLeXCD4T cells comprise a subpopulation expressing high levels of Th2 and Th17 cytokines, chemokine receptors CCR4 and CCR6, and the transcription factors GATA-3 and RORγT.

Ligation of the CD44 Glycoform HCELL on Culture-Expanded Human Monocyte-Derived Dendritic Cells Programs Transendothelial Migration.

The success of dendritic cell (DC)-based immunotherapeutics critically hinges on the capacity of the vascularly administered cells to enter tissues. Transendothelial migration (TEM) is dictated by an ordered cascade of receptor/ligand interactions. In this study, we examined the key molecular effectors of TEM of human monocyte-derived DCs (mo-DCs) generated by clinically relevant methods: CD14 selection (CD14-S) and plastic adherence selection (PA-S).

Neonatal hyperoxia leads to persistent alterations in NK responses to influenza A virus infection.

Respiratory distress in preterm or low birth weight infants is often treated with supplemental oxygen. However, this therapy can disrupt normal lung development and architecture and alter responses to respiratory insults. Similarly, exposure of newborn mice to 100% oxygen during saccular lung development leads to permanent alveolar simplification, and upon challenge with influenza A virus, mice exhibit reduced host resistance.

New insights into the role of the aryl hydrocarbon receptor in the function of CD11c⁺ cells during respiratory viral infection.

The aryl hydrocarbon receptor (AHR) has garnered considerable attention as a modulator of CD4(+) cell lineage development and function. It also regulates antiviral CD8(+) T-cell responses, but via indirect mechanisms that have yet to be determined. Here, we show that during acute influenza virus infection, AHR activation skews dendritic-cell (DC) subsets in the lung-draining lymph nodes, such that there are fewer conventional CD103(+) DCs and CD11b(+) DCs.

Differential consequences of two distinct AhR ligands on innate and adaptive immune responses to influenza A virus.

Immune modulation by the aryl hydrocarbon receptor (AhR) has been primarily studied using 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Recent reports suggest another AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ), exhibits distinct immunomodulatory properties, but side-by-side comparisons of these 2 structurally distinct, high-affinity ligands are limited. In this study, the effects of in vivo AhR activation with TCDD and FICZ were directly compared in a mouse model of influenza virus infection using 3 key measures of the host response to infection: pulmonary neutrophilia, inducible nitric oxide synthase (iNOS) levels, and the virus-specific CD8(+) T-cell response.

Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways.

Exposing preterm infants or newborn mice to high concentrations of oxygen disrupts lung development and alters the response to respiratory viral infections later in life. Superoxide dismutase (SOD) has been separately shown to mitigate hyperoxia-mediated changes in lung development and attenuate virus-mediated lung inflammation. However, its potential to protect adult mice exposed to hyperoxia as neonates against viral infection is not known.