While the role of vertebrate immune cytokines in infection control has been widely studied, their impact on tissue development and organ physiology remains poorly understood. We are addressing these questions by focusing on cytokines we found are active in the developing gut, and whose dysregulation is linked to inflammatory gut diseases in humans. These include IL-22 and IL-26, which are produced by innate lymphoid cells (ILCs) and other mucosal lymphocytes, and which target primarily epithelia.

- Role of IL-22 in post-embryonic gut development. We recently found that IL-22 modulates enteric nervous system function during early life. We identified hormone-producing enteroendocrine epithelial cells as the main source of il22 in the larval gut and that its expression is induced by metabolites from bacteria. We are currently deciphering the mechanisms by which IL-22 modulates gut neuronal activity and gut physiology.

- Deciphering the in vivo function of IL-26 in the developing gut. Very little is known about the in vivo function of IL-26 as it is absent in rodents, key models for studying vertebrate immune gene function. The zebrafish, however, has a single il26 gene. Using gain- and loss-of-function approaches, we revealed that IL-26 modulates cell proliferation, and DNA repair in the gut in a microbiota-dependent manner. We are currently determining the consequences of IL-26 dysregulation in epithelial cells at steady state and upon inflammation.

Blood cells are known to emerge in developmental waves, however, the function of wave-specific cells is not well understood. To dissect the role of immune cells derived from different waves in tissue development, homeostasis, and repair, we are developing new spatiotemporal tracing and wave-specific cell impairment/ablation tools. We are particularly interested in innate immune cells such as neutrophils, macrophages, and innate lymphoid cells (ILCs) because of their evolutionary conservation and broad rapid responses to tissue damage.