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. Lymph vessels may aggravate or ameliorate immune responses by transporting pro- or anti-inflammatory acting cells. Here, we focus on the conjunctival lymphatic vasculature, adjoining the lymphangiogenically privileged cornea 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 directly affect the distribution and trafficking of innate and adaptive immune cells, the precise micro-anatomy of the conjunctival lymphatic vessel bed remains unknown. Using light sheet fluorescence microscopy, we visualize the spatial microanatomy of murine conjunctival lymph vessels with cellular resolution.
We address the function of conjunctival lymph vessels in immune cell migration in a disease model of the 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 toxins may affect up to 0.1% of the population. Despite the substantial health impact, the nature of OPM remains enigmatic. In addition to two initially identified and molecularly cloned potentially allergenic proteins, termed thaumetopoeins, a large number of hypothetical toxin components have recently been proposed based on omics analysis. However, for none of the potential toxin components a direct allergenic activity has so far been established.
At the outset of this project, we succeeded to demonstrate a strong allergenic action of one of the initially identified thaumetopoeins, Tha p2. We are presently developing a murine model for Tha p2-induced allergy, which will allow us to address the role of DC migration during development and resolution of the OPM-toxin response. We focus on DCs as they have already been identified as efficient modulators of conjunctival allergy. Our investigation of the lymph vessel – DC axis in OPM 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
