Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome.

Area of Science:

• Immunology
• Microbiome Research
• Inflammation Biology

Background:

• Immune homeostasis relies on host-microbiome interactions.
• Interferon (IFN) signaling, via STAT1, manages acute infections.
• The role of tonic IFN in immune homeostasis is understudied.

Purpose of the Study:

• To investigate the function of tonic IFN signaling in maintaining immune homeostasis.
• To understand the impact of absent tonic IFN on the microbiome and immune cell populations.

Main Methods:

• Utilized STAT1 knockout (KO) mice to study the absence of tonic IFN signaling.
• Analyzed gut bacteria composition and immune cell profiles (T helper 17 and regulatory T cells).
• Employed antibiotic treatment to reduce bacterial load and IL17 signaling blockade.

Main Results:

• STAT1 KO mice developed spontaneous inflammatory disease, including myeloid hyperplasia and splenic hematopoietic stem cell accumulation.
• Absence of tonic IFN signaling led to gut dysbiosis, T_H17 cell expansion, and T_reg cell loss.
• Antibiotic treatment reversed T_H17 bias, and IL17 blockade prevented inflammatory phenotypes.

Conclusions:

• Tonic IFNs are critical regulators of gut microbial ecology.
• This microbial regulation by IFNs is essential for maintaining immune homeostasis and preventing inflammatory diseases.
• Targeting the microbiome or IL17 pathway may offer therapeutic strategies for inflammatory conditions.