IFN-β inhibits T cells accumulation in the central nervous system by reducing the expression and activity of chemokines in experimental autoimmune encephalomyelitis

Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders

“…Furthermore, IFN-g is needed to suppress infiltration of Th17 and is believed to decrease susceptibility in EAE development [138]. By contrast, IFN-b treatment improves EAE by impeding leukocyte influx [139]. For these reasons, identification of particular IFN effector genes responsible for the beneficial therapeutic properties is necessary.…”

IFN-β differentially regulates the function of T cell subsets in MS and EAE

“…Thorough investigation of the molecular mechanisms that underlie the beneficial effects of type I IFNs on each T cell subtype would be crucial for understanding the possibility of designing novel customized IFN-β-based therapies that selectively target and manipulate specific T cell subpopulation, thus possibly improving existing therapeutic interventions in MS. Expression of Th1 chemokines and their receptors on CD4 + T in the CNS [54] IFN-γ production by Th1 cells [53] ↓ ↓ ↑ Expression of T-bet and IFN-γ genes in the blood [43] CCR5 mRNA levels and its ligands on T cells [56] CCR5, IL-12Rβ2 and IFN-γ mRNA levels in PBMCs [57] Th17 ↓ ↓ ↓ IL-17 production by MOG-primed splenocytes [51] Frequency of CD4 + IL-17 + LN cells on day 4 of EAE [58] Frequency of CD4 + IL-17 + and CD4 + CCR6 + splenocytes and IL-17 production on day 10 of EAE [62] ↓ ↓ ↓ ↑ ↓ IL17 production by MOG-primed LN cells [28] IL17 mRNA levels in spleen and LN cells [37,64] Frequency of CD4 + IL-17 + cells in the brain [38] Production of IL-27 by DCs [38] Expression of Th17 chemokines and their receptors on CD4 + T cells in the CNS [54] ↓ IL-17A and IL-17F production by CD4 + T cells in PBMCs [63] ↓ ↓ ↓ ↓ Th17 cells differentiation in PBMCs [61,65] IL-17 mRNA and protein levels in PBMCs [66,67] Proportion of IL-17A + and IL-17F + CD4 + T cells in PBMCs [63] Expression of IL17C and IL23R genes in PBMCs [63] Tregs ↑ ↑ ↑ IL-10 production by splenocytes [28] IL-10 mRNA levels in PLP-specific T cells and IL-10 protein in PLP-primed LN cells [40] Treg proliferation [72] ↑ IL-10 and Foxp3 mRNA levels in serum and CSF [80] ↑ ↑ ↑ ↑ ↑ Treg function and proportion in peripheral blood [73] IL-10 mRNA and protein levels in PBMCs [40,82] IL-10 production by CD4 + T cells in PBMCs [65] IL-10 + cells in PBMCs [67,…”

“…Besides the role of endogenous IFN-β in EAE and MS, exogenous IFN-β decreased IL-17 production by MOG-primed LN cells in vitro [28] and lessened IL-17 mRNA levels in LN and spleen cells from EAE mice [37,64]. In accordance with these results, Sweeney et al detected lower frequency of CD4 + IL-17 + cells in the brain of EAE mice, treated daily with recombinant IFN-β, accompanied by increased levels of IL-27 [38].Furthermore, in vivo treatment with IFN-β during EAE significantly reduced the absolute numbers of CD4 + T cells expressing the Th17 characteristic chemokine receptors CCR2, CCR4 and CCR6 in the CNS, indicating that IFN-β decreases Th17 cell infiltration into the CNS [54].…”

“…Moreover, it was recently suggested that exogenous IFN-β can directly suppress in vitro IFN-γproduction by Th1 cells in EAE partly due to the induction of the negative regulatory receptor TΙΜ-3 on effector Th1 cells [53]. Apart from their capacity to produce IFN-γ, Th1 cells also express characteristic chemokine receptors, such as CCR5 and CXCR3 [54]. A recent study demonstrated that, in vivo treatment with IFN-β during EAE decreased the absolute numbers of infiltrated CD4 + T cells expressing these receptors, along with reduced Th1 migration into the CNS [54].…”

“…Apart from their capacity to produce IFN-γ, Th1 cells also express characteristic chemokine receptors, such as CCR5 and CXCR3 [54]. A recent study demonstrated that, in vivo treatment with IFN-β during EAE decreased the absolute numbers of infiltrated CD4 + T cells expressing these receptors, along with reduced Th1 migration into the CNS [54]. Furthermore, IFN-β is shown to directly impair the encephalitogenicity of Th1 cells, since they are not capable to induce EAE when transferred into Rag1 -/-mice [53].…”