Crohn's disease: innate immunodeficiency?

Abstract

In the past, Crohn's disease (CD) has been understood primarily as an immunologic disorder characterized by an abnormal T-cell response. Recent in vitro and in vivo data suggests that CD may instead be precipitated by innate immune dysfunction resulting from a combination of genetic and environmental factors. Some reports have demonstrated a defective immune response in a variety of other cellular components, including neutrophils, monocytes and dendritic cells. Recent studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD, aiming to stimulate the innate immune system with the conception that an innate immune defect underlies the development of the disease, have been demonstrated a clinical benefit and reinforce this evolving understanding of the disease.

Figure 1

Impairment of different innate immune mechanisms. These mechanisms play a central role in the homeostasis of intestinal barrier function. Identified environmental risks and genetic susceptibility may contribute to the innate immune dysfunction.

Figure 2

Targets of immunostimulation therapy in Crohn’s disease. Potential therapies encompass interventions focused on augmenting the intestinal innate immune function in different mechanisms of action.