Docosahexaenoic acid supplementation aggravates myasthenia gravis through immune dysregulation.

Mendelian randomization identified elevated serum DHA levels as a causal risk factor for myasthenia gravis.

• Mendelian randomization was used to establish causal relationships between serum metabolites and MG.
• Dysregulated lipid metabolism, particularly elevated DHA levels, was identified as a significant risk factor for MG.
• DHA levels were found to influence various markers associated with Treg cells in MG patients.

Dietary supplementation with 1% DHA exacerbated disease severity in experimental autoimmune myasthenia gravis (EAMG) rats.

• Rats received dietary intervention with 1% DHA added to their diet.
• DHA supplementation worsened the progression of EAMG in the rat model.
• The exacerbation was accompanied by enhanced B cell immune responses and promoted antibody production.

DHA supplementation enhanced B cell immune responses and promoted antibody production in EAMG rats.

• The addition of 1% DHA to the diet enhanced B cell immune responses in EAMG rats.
• DHA supplementation promoted antibody production in the EAMG model.
• These effects contributed to the aggravated disease severity observed with DHA treatment.

DHA supplementation increased the proportion of Treg cells in EAMG rats despite worsening disease.

• Despite exacerbating EAMG severity, DHA supplementation led to an increase in the proportion of Treg cells.
• This paradoxical finding suggested that increased Treg cell numbers did not translate to improved disease control.
• The increase in Treg cell proportion occurred alongside enhanced B cell activity and antibody production.

DHA accumulation in Treg cells enhances their proliferation but impairs their inhibitory function through the PI3K-Akt signaling pathway.

• In vitro experiments confirmed that DHA accumulation in Treg cells enhances their proliferation.
• DHA accumulation in Treg cells impairs their inhibitory function.
• The impairment of Treg inhibitory function was mediated partially through the PI3K-Akt signaling pathway.
• Metabolomic and transcriptomic analyses of Treg cells were performed during MG progression to support these findings.

Metabolomic and transcriptomic analyses of Treg cells revealed alterations associated with MG progression.

• Metabolomic analyses of regulatory T cells (Treg) were conducted during MG progression.
• Transcriptomic analyses of Treg cells were also performed during MG progression.
• These analyses provided mechanistic insight into how DHA affects Treg cell function in the context of MG.