Project: B04

Variability and organ specificity of lymphatic vessel – dendritic cell interactions in the eye (allergic conjunctivitis)

Lymphatic vessels are increasingly recognized for their specific roles in the support of organ function and the prevention of pathologies. Here, we focus on the conjunctival lymphatic vasculature and its role in immune cell migration in particular dendritic cell (DC) migration, which is implicated in allergic eye disease. Despite its important function and capacity to affect the distribution and trafficking of innate and adaptive immune cells directly, the precise micro-anatomy of the conjunctival lymphatic vessel bed remains unknown. Lymph vessels may aggravate or ameliorate immune responses depending on whether they transport pro- or anti-inflammatory acting cells.

Using light sheet fluorescence microscopy, we will image the complete murine conjunctival lymph vessel bed with cellular resolution in mouse strains with a strong and a weak natural lymphangiogenic ocular response.

We will address immune cell migration in a disease model of oak processionary moth (OPM) toxin-elicited conjunctivitis that is poorly investigated and mechanistically not understood. OPM outbreaks cause dermal, ophthalmic, and respiratory health problems that have been attributed to exceptionally stable toxins in the burn hairs of OPM caterpillars. In strongly infested areas OPM may affect up to 0.1% of the population. Despite this impact, only two highly related allergenic proteins, termed thaumetopoeins, have been identified and molecularly cloned in the closely related pine processionary moth so far. Moreover, their biological activity has not yet been investigated.

Dendritic cells (DCs) have already been identified as efficient modulators of conjunctival allergy. Therefore, we focus on this immune cell type and address DC migration during development and resolution of the OPM-toxin response. Our investigation of the lymph vessel – DC axis in allergic conjunctivitis is motivated by the aim to identify new opportunities for treatment interventions.

Key methods: in vivo conjunctivitis model, intravital multiphoton microscopy (MPM), light sheet fluorescence microscopy, immunohistochemistry, ELISA