Effect of tick saliva cystatins on Th9 cells, mast cells and the development of experimental asthma

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Tick saliva contains an array of immunomodulatory molecules facilitating both blood feeding and tick-borne pathogen transmission. Based on cDNA library of tick salivary glands, some of these molecules have been identified and prepared by recombinant expression. Ixodes ricinus tick saliva and sialostatin L, a cystatin isolated from saliva of the related tick I. scapularis, surprisingly inhibited production of interleukin 9 (IL-9). As IL-9 plays a central role in the development of allergic asthma, we administered sialostatin L during the sensitization phase in a murine asthma model and found in pilot experiments that it inhibits the development of this disease. Since our preliminary data demonstrated that sialostatin L has a substantial inhibitory capacity on the IL-9 production of mast cells and Th9 cells, we will primarily focus on the inhibitory mechanism(s) of such cystatins. Especially, the influence of cystatins on the kinome of Th9 cells and mast cells will be analyzed. Alternatively, expression profiles of Th9 cells and mast cells will be determined by next-generation sequencing (NGS) in the absence and presence of inhibitory cystatins. Eventually, the obtained results will be used to develop innovative therapeutic strategies for the treatment of allergic diseases and asthma by exploiting definite IL-9 modulating molecules from tick saliva.