Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells

Langerhans cells (LCs) represent a special subset of immature dendritic cells (DCs) that reside in epithelial tissues at the environmental interfaces. Although dynamic interactions of mature DCs with T cells have been visualized in lymph nodes, the cellular behaviours linked with the surveillance of tissues for pathogenic signals, an important function of immature DCs, remain unknown. To visualize LCs in situ, bone marrow cells from C57BL/6 mice expressing the enhanced green fluorescent protein (EGFP) transgene were transplanted into syngeneic wild-type recipients. Motile activities of EGFP(+) corneal LCs in intact organ cultures were then recorded by time lapse two-photon microscopy. At baseline, corneal LCs exhibited a unique motion, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of their dendritic processes through intercellular spaces between epithelial cells. Upon pinpoint injury produced by infrared laser, LCs showed augmented dSEARCH and amoeba-like lateral movement. Interleukin (IL)-1 receptor antagonist completely abrogated both injury-associated changes, suggesting roles for IL-1. In the absence of injury, exogenous IL-1 caused a transient increase in dSEARCH without provoking lateral migration, whereas tumour necrosis factor-alpha induced both changes. Our results demonstrate rapid cytokine-mediated behavioural responses by LCs to local tissue injury, providing new insights into the biology of LCs.