Project: TAK1 Impact on Microbiome Structure
University Association: The Methodist Hospital Research Institute
Collaborator Name: Rongfu Wang
TGF-β activated kinase-1 (TAK1) is a critical upstream kinase and regulator of NF-κB and mitogen-activated protein kinase (MAPK) signaling during innate immune responses to pathogens. Specific deletion of TAK1 in myeloid cells (Map3k7ΔM/ΔM) led to development of splenomegaly and lymphomegaly associated with neutrophilia. In addition, LPS stimulation enhanced the phosphorylation of the NF-κB and MAPKs in neutrophils and caused hypersensitivity to septic shock in TAK1-deficient mice.
Therefore, we conclude that TAK1 is essential for NF-κB activation in T and B cells but has precisely the opposite activity in myeloid cells where it acts as a negative regulator in a cell type-specific manner. Based on the evidence that TAK1 is critical for proinflammatory signaling in myeloid cells, we are investigating whether the proinflammatory microenvironment in TAK1-deficient mice alters the gut microbiota and influences intestinal homeostasis.