The TRAF6-NFκB signaling pathway in autoimmunity: not just inflammation

Excerpt

Recently, Akiyama et al . [1] described defects in thymic negative selection and in CD4⁺CD25⁺ regulatory T cell production in mice deficient for tumor necrosis factor (TNF) receptor associated factor (TRAF)6. Signaling through cell surface receptors to activate nuclear factor (NF)κB and mitogen-activated protein (MAP) kinases through adaptor molecules, including TRAF6, is of critical importance to survival and activation of all cells in the body, from those regulating the immune response to epithelial cells, with which immunocytes interact (Fig. 1). Because the same cell signaling pathways regulate survival and activation in the periphery and in the thymus, however, mutations or polymorphisms in the pathway can have outcomes for the immune system that might have been difficult to predict. This is because survival and activation of key antigen presenting cells (APCs), medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), involved in thymic negative selection and peripheral immunity are regulated by a similar network of genes, which map a pathway from TRAF6 to the NFκB family member RelB.

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