Dendritic cells & IL-23/12

Dendritic cells & IL-23/12

Role of Dendritic Cells in Lung Ischemia-Reperfusion Injury

PI:  Victor Laubach, PhD

Dendritic cells (DCs) and macrophages are principle cell types involved in both innate and adaptive immunity and characteristically comprise the CD11c+ population of cells within the lung (DCs: CD11chighCD11bhigh, macrophages: CD11chighCD11blow). Pulmonary DCs may be further characterized as distinct subsets: CD103+ and CD11bhi, with CD103+ DCs predominantly eliciting Th1 and Th17 responses and CD11bhi DCs provoking Th2 responses under the steady state. Despite this understanding, the differential activity of these subsets in acute inflammation and, more specifically, lung IR injury are undefined.

IL-12 and IL-23 are products of activated DCs and macrophages and belong to the same cytokine family, sharing the p40 subunit yet demonstrating distinct biologic activities.  IL-12 is considered a principle activator of cell-mediated immunity with biologic activity only as a composite factor of p35 and p40 subunits (p70), while the related IL-23 cytokine is comprised of p19 and p40 subunits.  IL-12 and IL-23 provide a principle link between innate and adaptive immunity, determining Th1 and Th17 cell-directed responses.

We are currently evaluating the contribution of CD11c+ DCs and macrophages in the early innate immune response in lung IR injury and assessing the potential contribution of the IL-23/IL-12 axis in effector cell activation and injury pathogenesis.