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

• Published in: Scientific reports Vol. 7; no. 1; pp. 12518 - 10
• Main Authors: Hartlehnert, Maike, Derksen, Angelika, Hagenacker, Tim, Kindermann, David, Schäfers, Maria, Pawlak, Mathias, Kieseier, Bernd C., Meyer zu Horste, Gerd
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.10.2017; Nature Publishing Group
• Subjects: 13/51; 631/250/21/1293; 631/250/21/324/1508; 631/378/1689/2610; 64/110; Antigen-presenting cells; Antigens; Axons; CD4 antigen; Cell activation; Clonal deletion; Helper cells; Humanities and Social Sciences; Immune response; Inflammation; Lymphocytes T; Major histocompatibility complex; multidisciplinary; Pain; Pain perception; Peripheral nerves; Peripheral neuropathy; Preservation; Rodents; Schwann cells; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-12744-2

The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (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 cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo . Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cells in mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic pain using the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia and, to a lesser extent, also diminishes mechanical allodynia in 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 cells by MHC-II on Schwann cells thus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cells gain antigen-presenting function in vivo and modulate local immune responses and diseases in the peripheral nerves.