CXCL10 Signaling Drives Chronic Inflammation in Arthritogenic Alphavirus Infections
Researchers identified that CXCL10-driven STAT3 signaling promotes pathogenic CD4+ T cell responses during arthritogenic alphavirus infections (including chikungunya and Mayaro viruses), limiting antiviral immunity. This mechanism was demonstrated across multiple alphaviruses in an age-stratified mouse model and involves skewed T cell differentiation that favors inflammation over viral clearance. Understanding this pathway could inform therapeutic strategies to reduce chronic joint disease caused by these viruses.
A bioRxiv preprint describes how arthritogenic alphaviruses—including onyong nyong, chikungunya, and Mayaro viruses—trigger a CXCL10-biased immune response that paradoxically increases inflammation while impairing viral clearance. Using age-stratified murine models, researchers found that infection induced elevated CXCL10 expression and viral persistence, accompanied by preferential CD4+ T cell accumulation and limited CD8+ T cell recruitment. This skewed immune response was characterized by increased STAT3 phosphorylation and RORγt expression, promoting a proinflammatory but ineffective antiviral state. Perturbation of the CXCL10-STAT3 axis reduced CD4+ T cell accumulation, altered T cell differentiation, and decreased tissue viral burden. The findings suggest this CXCL10-driven pathogenic program is conserved across arthritogenic alphaviruses and may explain the transition from acute to chronic inflammatory joint disease.
What's missing
The preprint does not specify whether findings have been validated in human subjects or primary human immune cells, nor does it detail the specific age ranges tested or how age-dependent mechanisms might translate to human disease. The study's limitations regarding the generalizability of murine models to human alphavirus infections are not explicitly discussed in the provided abstract.
What different sources said
- bioRxivCenter
CXCL10-driven STAT3 signaling programs pathogenic CD4+ T cell responses and limits antiviral immunity during arthritogenic alphavirus infection
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