| First Author | Zhang G | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 8 | Pages | e0220250 |
| PubMed ID | 31415574 | Mgi Jnum | J:279101 |
| Mgi Id | MGI:6356221 | Doi | 10.1371/journal.pone.0220250 |
| Citation | Zhang G, et al. (2019) Elimination of activating Fcgamma receptors in spontaneous autoimmune peripheral polyneuropathy model protects from neuropathic disease. PLoS One 14(8):e0220250 |
| abstractText | Spontaneous autoimmune peripheral polyneuropathy (SAPP) is a reproducible mouse model of chronic inflammatory peripheral neuropathy in female non-obese diabetic mice deficient in co-stimulatory molecule, B7-2 (also known as CD86). There is evidence that SAPP is an interferon-gamma, CD4+ T-cell-mediated disorder, with autoreactive T-cells and autoantibodies directed against myelin protein zero involved in its immunopathogenesis. Precise mechanisms leading to peripheral nerve system inflammation and nerve injury including demyelination in this model are not well defined. We examined the role of activating Fc-gamma receptors (FcgammaRs) by genetically ablating Fcgamma-common chain (Fcer1g) shared by all activating FcgammaRs in the pathogenesis of this model. We have generated B7-2/ Fcer1g-double null animals for these studies and found that the neuropathic disease is substantially ameliorated in these animals as assessed by behavior, electrophysiology, immunocytochemistry, and morphometry. Our current studies focused on characterizing systemic and endoneurial inflammation in B7-2-null and B7-2/ Fcer1g-double nulls. We found that accumulation of endoneurial inflammatory cells was significantly attenuated in B7-2/ Fcer1g-double nulls compared to B7-2-single nulls. Whereas, systemically the frequency of CD4+ regulatory T cells and expression of immunosuppressive cytokine, IL-10, were significantly enhanced in B7-2/ Fcer1g-double nulls. Overall, these findings suggest that elimination of activating FcgammaRs modulate nerve injury by altering endoneurial and systemic inflammation. These observations raise the possibility of targeting activating FcgammaRs as a treatment strategy in acquired inflammatory demyelinating neuropathies. |
