High Ambient Temperature Aggravates Experimental Autoimmune Uveitis Symptoms.

Area of Science:

• Immunology
• Environmental Health

Background:

• Ambient temperature's impact on immune-mediated diseases like uveitis remains largely unexplored.
• Understanding environmental factors influencing autoimmune conditions is crucial for disease management.

Purpose of the Study:

• To investigate the effect of ambient temperature on experimental autoimmune uveitis (EAU) severity in mice.
• To elucidate the underlying immunological mechanisms, including T-cell responses and neutrophil extracellular traps (NETs).

Main Methods:

• Mice were housed at normal (22°C) or high (30°C) temperatures before EAU induction.
• Uveitis severity was assessed histologically.
• Flow cytometry, qPCR, and ELISA were used to measure immune cell frequencies, cytokine expression, and NETs.
• Metabolomic analysis identified key plasma metabolites, which were tested in vitro.

Main Results:

• High ambient temperature significantly worsened uveitis pathology.
• Elevated frequencies of Th1 and Th17 cells and increased IFN-γ/IL-17A mRNA were observed at higher temperatures.
• Neutrophil extracellular trap (NET) markers (MPO, NE) were significantly higher in high-temperature EAU mice.
• Fumaric and succinic acids, elevated at high temperatures, induced NETs via NADPH oxidase but did not affect T-cell differentiation.

Conclusions:

• Increased ambient temperature is a risk factor for developing uveitis.
• The exacerbation of EAU at higher temperatures is linked to enhanced Th1/Th17 responses and NET formation.
• The NADPH oxidase pathway plays a role in temperature-mediated NET generation.