Table 5.
Molecules and pathways implicated in sex differences in EAE.
| Molecule/Pathway | Model | Effect | References |
|---|---|---|---|
| ApoE | MOG35-55-induced EAE in C57BL/6 wildtype or apoE-deficient mice | Apo E deficiency led to less severe disease in males but more severe EAE in females compared to wildtype mice. | (85) |
| Axonal injury markers | MOG35-55-induced EAE in C57BL/6 mice | Greater axonal amyloid precursor protein (APP) and non-phosphorylated neurofilament heavy chain expression and greater dendritic branching in males vs females | (86) |
| CD152 (CTLA-4) | PLP139-151-immunized SJL mice | Activated Th cells from females have reduced expression of CD152 (CTLA4) compared to males | (87) |
| Complement | MOG35-55-induced EAE in C57BL/6 mice | Greater complement expression in optic nerves of females; associated with greater axonal loss in females | (82) |
| Cystatin C (Cst3) | MOG35-55-induced EAE in Cst3 null C57BL/6 mice | No effects in males. Females showed reduced severity of clinical signs of EAE, which was associated with lower expression of molecules involved in T cell activation. | (88) |
| HuR | MOG35-55-induced EAE in C57BL/6 mice expressing the RNA regulator HuR | Less severe disease in female HuR+ mice compared to wildtype females. Effect due to gonadal hormones. | (81) |
| IFN-γ | PLP139-151-induced EAE in SJL mice | Lymph node and spleen cells from female mice produce more IFN-γ and are more pathogenic than male cells. | (76) |
| IL-13 | PLP139-151-induced EAE in SJL-cKit mutant mice | Males have increased susceptibility, due to decrease in IL-13 production by ILC2 cells and switch from Th2 to Th17 response. Females more resistant to EAE development. | (77) |
| IL-13 | MOG35-55-induced EAE in IL13C57BL/6 mice | Knockout or IL-13 reduced incidence and severity of EAE in females but not males. | (50) |
| IL-17 | PLP139-151-induced EAE in SJL mice and MOG35-55-induced EAE in C57BL/6 mice | Male mice produce more IL-17 than females | (75, 76) |
| IL-33 | PLP139-151- induced EAE in SJL mice | IL-33 selectively induced in androgen-responsive mast cells in males, which activates ILC2 to promote and sustain a Th2 type of response and prevent EAE. Treatment of female mice with IL-33 reduces disease in females. Treatment of male mice with anti-IL-33 antibody made them more susceptible to EAE. | (79) |
| MBP | gpSCH-induced EAE in DA rats | Sex difference in MBP expression during remyelination | (47) |
| iNOS/NO | MBP-induced EAE in PVG rats | Females resist EAE with increased NO production by macrophages | (63) |
| iNOS/NO | Passive transfer of MBP-specific T cells in SJL mice | T cells from female donors induced more severe disease and higher expression of iNOS and NO in female vs male recipients. T cells from male donors induced only mild disease with no iNOS or NO. | (89) |
| Oxidative stress markers | Rat SCH-induced EAE in DA rats | Males had increased markers of oxidative stress | (90) |
| p38MAP kinase | MOG35-55-induced EAE in C57BL/6 mice | Inhibition reduced EAE in females, not males | (91) |
| PDGF alpha receptor | gpSCH-induced EAE in DA rats | Sex differences in expression during remyelination | (47) |
| S1P receptor 2 | PLP139-151-induced EAE in SJL mice and MOG35-55-induced EAE in C57BL/6 mice | Increased expression in SJL females vs males, leading to enhanced vascular permeability in CNS tissue of females but not males. Equal expression in both sexes in C57BL/6 mice with MOG-induced EAE | (92) |
| TLR7 | Bone marrow chimeric SJL-FCG mice with PLP-EAE | Presence of XY sex complement in the CNS leads to more severe EAE, due to increased expression of TLR7 in the CNS | (93) |
| Vitamin D metabolism | gpMBP-induced EAE in B10.PL(73NS)/Sn mice | Vitamin D3 protective in female but not male mice; females have enhanced ability to metabolize Vitamin D3 to active hormone | (94) |