ATF3 Stimulates IL-17A by Regulating Intracellular Ca

Area of Science:

• Immunology
• Microbiology
• Cellular Biology

Background:

• Activating transcription factor-3 (ATF3) is involved in immune responses to bacterial infections.
• Interleukin-17A (IL-17A) is vital for eliminating Streptococcus pneumoniae.
• The precise mechanism linking ATF3 to IL-17A production is not fully understood.

Purpose of the Study:

• To elucidate the mechanism by which ATF3 induces IL-17A production.
• To investigate the role of ATF3 in host defense against Streptococcus pneumoniae.

Main Methods:

• Utilized ATF3 knockout (KO) mice and wild-type (WT) mice.
• Measured IL-17A protein and mRNA expression.
• Assessed mitochondrial IL-1β secretion, reactive oxygen species (ROS), and Ca2+ homeostasis in macrophages.
• Evaluated survival rates and bacterial clearance post-infection.

Main Results:

• ATF3 deficiency significantly reduced IL-17A production.
• ATF3 induced IL-17A via NLRP3 inflammasome-dependent IL-1β secretion.
• ATF3 disruption impaired ROS and Ca2+ homeostasis, reducing IL-1β production.
• ATF3 KO mice showed decreased survival and bacterial clearance.

Conclusions:

• Macrophage ATF3 promotes IL-17A production in γδ T cells.
• This pathway is critical for early host defense against Streptococcus pneumoniae.
• ATF3 plays a key role in regulating IL-17A-mediated immunity.