TWEAK is expressed by glial cells, induces astrocyte proliferation and increases EAE severity

Area of Science:

• Neuroimmunology
• Molecular and Cellular Biology
• Inflammation Research

Background:

• Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a cytokine with known proinflammatory and proliferative effects.
• TWEAK mediates its functions through the Fn14 receptor, recently identified.
• The role of TWEAK and Fn14 in the central nervous system (CNS) remains to be fully elucidated.

Purpose of the Study:

• To investigate the expression and role of TWEAK and its receptor Fn14 in mouse microglial cells and astrocytes.
• To determine the impact of TWEAK on CNS inflammation, specifically in the context of experimental autoimmune encephalomyelitis (EAE).

Main Methods:

• Analysis of TWEAK mRNA expression in mouse microglial cells and astrocytes.
• Assessment of Fn14 expression on astrocytes.
• Evaluation of astrocyte proliferation in response to recombinant TWEAK (rTWEAK).
• Measurement of TWEAK mRNA levels in the spinal cord during EAE.
• Comparison of EAE severity in wild-type and soluble TWEAK-overexpressing transgenic mice.

Main Results:

• Both mouse microglial cells and astrocytes express TWEAK mRNA.
• Astrocytes express Fn14 and demonstrate proliferation upon stimulation with rTWEAK.
• TWEAK mRNA is present in the normal CNS, with increased levels in the spinal cord during EAE.
• Mice overexpressing soluble TWEAK exhibit enhanced EAE severity.

Conclusions:

• TWEAK and its receptor Fn14 are expressed in key glial cells within the CNS.
• TWEAK influences astrocyte proliferation, suggesting a role in CNS cellular responses.
• Elevated TWEAK levels correlate with and exacerbate CNS inflammation during EAE.
• These findings strongly support the involvement of the TWEAK/Fn14 pathway in neuroinflammation.