FOR2599Project 4

Tissue recruitment of type 2 effector cells

Summary

The recruitment of type 2 effector cells into barrier tissues like skin and lung is regulated by complex signals and interaction of adhesion molecules that work in concert to regulate extravasation at sites of barrier defects and inflammation.

In this project we study the mechanisms which regulate development and tissue recruitment of IL-4/IL-13-expressing effector cells such as eosinophils, basophils, type 2 innate lymphoid cells and T helper 2 cells during type 2 immune responses in lung and skin. We analyze the requirement of STAT6-regulated genes in various hematopoietic cell types, endothelial cells or epithelial cells and keratinocytes for regulation of effector cell recruitment in the context of type 2 immune responses. We further study how deletion of individual genes encoding integrins and other adhesion proteins in eosinophils or basophils affects their tissue migration. Finally, we investigate the role of alternatively activated macrophages in type 2 immune responses and wound healing in lung and skin.

By this approach we hope to identify new STAT6-dependent and –independent pathways of tissue-specific accumulation of type 2 effector cells which could be targeted in a therapeutic setting to ameliorate allergic inflammation in lung and skin.