Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain

Area of Science:

• Neuroimmunology
• Cytokine signaling

Background:

• Multiple sclerosis (MS) is a CNS inflammatory and demyelinating disease.
• Cytokines regulate MS pathogenesis; Interleukin-9 (IL-9) shows anti-inflammatory and neuroprotective effects in MS patients.

Purpose of the Study:

• Investigate IL-9 expression in the CNS in MS.
• Elucidate mechanisms of IL-9's effects on CNS-infiltrating immune cells.

Main Methods:

• Analyzed IL-9 and IL-9 receptor (IL-9R) expression in post-mortem MS CNS samples.
• Utilized immunohistochemistry, flow cytometry, and western blot.
• Assessed IL-9's impact on immune cell signaling and function.

Main Results:

• IL-9 and IL-9R are expressed in the MS brain, notably on macrophages, microglia, and CD4 T lymphocytes.
• IL-9 reduced activation markers and promoted anti-inflammatory properties (TGF-β secretion) in macrophages.
• In situ, elevated IL-9 correlated with reduced activated macrophages.

Conclusions:

• IL-9 is a novel cytokine expressed in the CNS with a role in MS.
• IL-9 modulates human macrophage activation and promotes anti-inflammatory functions.
• Targeting IL-9 may offer a therapeutic strategy for MS.