NFAT5 contributes to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and decrease of T regulatory...

Area of Science:

• Neuroimmunology
• Immunogenetics

Background:

• Multiple sclerosis (MS) disproportionately affects women.
• Experimental autoimmune encephalomyelitis (EAE) serves as a model for MS pathogenesis.
• The role of NFAT5 in EAE and its sex-specific contribution remains unclear.

Purpose of the Study:

• To investigate the role of NFAT5 in the pathogenesis of EAE.
• To determine if NFAT5's impact on EAE is sex-associated.

Main Methods:

• Utilized NFAT5 haplodeficiency in a mouse model of EAE.
• Analyzed immune cell populations, specifically T regulatory (Treg) cells and dendritic cells, in the CNS and spleen.
• Assessed disease severity in relation to NFAT5 status and sex.

Main Results:

• NFAT5 haplodeficiency significantly reduced EAE disease severity exclusively in female mice.
• This reduction correlated with a notable increase in the frequency of Treg cells in both the CNS and spleen of female mice.
• NFAT5 haploinsufficiency decreased the frequency of CD11c+CD8α+ dendritic cells in the female CNS.

Conclusions:

• NFAT5 plays a significant role in the pathogenesis of EAE, particularly in female mice.
• The protective effect of NFAT5 deficiency in females may be mediated by an increased frequency of tissue-specific Treg cells.
• NFAT5 influences immune cell populations relevant to EAE pathogenesis in a sex-dependent manner.