α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow-Derived Non-T Cells Is Required for the Inflammatory Reflex

The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease, This mechanism, the inflammatory reflex, requires the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of alpha 7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and alpha 7nAChR-deficient mice. Deficiency of alpha 7nAChR in bone marrow-derived cells significantiy impaired vagus nerve-mediated regulation of tumor necrosis factor (TNF), whereas alpha 7nAChR deficiency in neurons and other cells had no significant effect. In agreement with recent work, the inflammatory reflex was not functional in nude mice, because functional T cells are required for the integrity of the pathway. To investigate the role of T-cell alpha 7nAChR, we adoptively transferred alpha 7nAChR-deficient or WIT cells to nude mice. Transfer of WT and alpha 7nAChR-deficient T cells restored function, indicating that alpha 7nAChR expression on T cells is not necessary for this pathway, Together, these results indicate that alpha 7nAChR expression in bone marrow-derived non-T cells is required for the integrity of the inflammatory reflex. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00405