The effect of LPS on CD103 expression on dendritic cells

Abstract

Abstract Control of the intensity and duration of the pulmonary immune response is crucial in homeostasis maintenance in the lung. Dendritic cells (DCs), the main antigen presentation population in the lung, play a crucial role in these mechanisms. Notably, CD103+ DCs play a regulatory role while CD11b+ DCs are considered pro-inflammatory cells. Therefore, the balance between these two important DC populations is crucial in homeostasis maintenance and host-defense. However, the mechanisms regulating this tight balance remain poorly understood. Preliminary data obtained in our laboratory showed that Saccharopolyspora rectivirgula exposure downregulates CD103+ DCs levels in vivo as early as 18h following antigen exposure, impacting the pro/anti-inflammatory DC balance. However, the mechanisms involved in this response are still undefined. As TNF is an important pro-inflammatory cytokine secreted rapidly in response to antigens (such as LPS), lung- and spleen-isolated DCs were stimulated in vitro for 18h with increasing concentrations of TNF and LPS. Flow cytometry and qRT-PCR analysis demonstrated that CD103 protein and mRNA expression are downregulated following stimulation. The percentage of CD103+ DCs was also decreased in vivo 18h after mouse LPS exposure (mouse model). Furthermore, exposure of Cd103−/− mice to LPS led to an impaired resolution of airway inflammation and return to homeostasis, supporting the importance of CD103 expression for homeostasis maintenance in the lung in response to antigens. Our results suggest that modulation of CD103 expression in response to antigens is a crucial step in host defense and homeostasis maintenance in the lung.