Innate immune control of pulmonary dendritic cell trafficking

Abstract

Dendritic cells (DC) are potent antigen-presenting cells that are essential for initiating adaptive immune responses. Residing within the airway mucosa, pulmonary DC continually sample the antigenic content of inhaled air and migrate to draining lymph nodes, where they present these antigens to naive T cells. The migratory patterns of pulmonary DC are highly dependent upon inflammatory conditions in the lung. Under steady-state, or non-inflammatory, conditions, pulmonary DC undergo slow but constitutive migration to draining lymph nodes, where they remain for several days and confer antigen-specific tolerance. With the onset of pulmonary inflammation, airway DC trafficking increases dramatically, and these cells rapidly accumulate within draining lymph nodes. However, within a few days, the number of airway-derived DC in lymph nodes stabilizes or declines, even in the face of ongoing pulmonary inflammation. Here, we summarize current understanding of the molecular and cellular mechanisms underlying pulmonary DC trafficking to the lymph node and the recruitment of DC precurors to the lung. It is hoped that an improved understanding of these mechanisms will lead to novel DC-mediated therapeutic strategies to treat immune-related pulmonary disease.

Figure 1.

Life cycle of pulmonary dendritic cells (DC). DC precursors exit the bone marrow and travel in the circulation to the lung, where they establish residence. Under steady-state conditions, pulmonary DC migrate constitutively to draining thoracic lymph nodes and present pulmonary antigens to naive T cells.

Figure 2.

Pulmonary DC trafficking is increased by innate immune stimuli. Antigen-bearing DC migration increases in both speed and volume after pulmonary exposure to a variety of innate immune–stimulating agents in the environment. This leads to an initial increase in the number of airway-derived DC in the lymph node, but this increase is short lived.