Mucosal immunologyNov 22, 2025

IL-10 signaling’s role in daily rhythms of the body’s response to flu infection

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

Blocking IL-10 signaling increased immunopathology during influenza A virus infection.

IL-10 signaling appears to be crucial for time-of-day-specific protection against influenza A virus.
Inhibition of IL-10 signaling led to greater lymphocyte infiltration and overall immune activation.
Later IL-10 receptor blockade removed the time-of-day differences in infection outcomes but improved results for mice infected at dusk.
Natural Killer cells may play a role in regulating IL-10 levels during the immune response to influenza A virus.
The findings highlight the importance of considering circadian rhythms in understanding immune responses to viral infections.

Simplified

We have previously demonstrated that the circadian clock regulates the host response to influenza A virus (IAV) infection. While IL-10 is well-known for its immunoregulatory function, its role in IAV remains unclear, with studies reporting both protective and detrimental effects. Given the diurnal rhythmicity of IL-10 receptor (IL-10ra) expression in the lung, we investigated the contribution of IL-10 signaling to time-of-day-specific IAV protection. We found that blocking IL-10 signaling abrogated the time-of-day protection, leading to increased immunopathology characterized by enhanced lymphocyte infiltration and global immune activation (transcriptomic analysis). Interestingly, while later, IL-10R blockade also eliminated the time-of-day difference in IAV outcomes, it improved the outcome of dusk-infected mice. Furthermore, Natural Killer (NK) cell depletion suppressed IL-10 levels in bronchoalveolar lavage, suggesting a role for these cells in regulating IL-10 signaling. In conclusion, incorporating the circadian context has not only clarified the IL-10 role in IAV infection but also underscored the pivotal influence of circadian regulation on immune responses.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Funding

Competing interests

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

IL-10 signaling’s role in daily rhythms of the body’s response to flu infection

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief