The MHC class II transactivator affects local and systemic immune responses in an α-synuclein seeded rat model for Parkinson’s disease

Parkinson’s disease (PD) is a heterogeneous disorder characterized by intraneuronal inclusions of alpha-synuclein (α-Syn), a strong neuroinflammatory component and neurodegeneration. Human genetic association studies have shown that variants affecting quantity and quality of major histocompatibility complex II (MHCII) have implications in PD susceptibility and it was recently shown that PD patients have α-Syn specific T lymphocytes in circulation. The class II transactivator (Ciita) is the major regulator of MHCII expression and reduced Ciita expression has been shown to increase α-Syn induced neurodegeneration and pathology in vivo. Here we show, using flow cytometry in an α-Syn overexpression model combined with α-Syn pre-formed fibrils (PFF), that congenic rats with naturally occurring differences in Ciita expression have altered local and peripheral immune populations. Lower Ciita levels are associated with increased percentages of microglia and circulating myeloid cells being MHCII+ but with lower levels of MHCII on individual cells. Additionally, lower Ciita levels was associated to higher TNF levels in serum, trends of higher CD86 levels in circulating myeloid population and a lower CD4/CD8 T lymphocyte ratio. Taken together, these results indicate that Ciita regulates serum TNF levels and baseline immune populations which could mediate an increased susceptibility to PD-like pathology.