Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II

The activation of T helper cellsrequires antigens to be exposed on the surface of antigen presentingcells (APCs) via MHC class II(MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cellsare potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cellshas not been studied in vivo. Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cellsin mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic painusing the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cellsreduces thermal hyperalgesiaand, to a lesser extent, also diminishes mechanical allodyniain CCI in female mice. This was accompanied by a reduction of intraneural CD4+ T cells and greater preservation of preferentially large-caliber axons. Activation of T helper cellsby MHC-II on Schwann cellsthus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cellsgain antigen-presentingfunction in vivo and modulate local immune responses and diseases in the peripheral nerves.