Interleukin-26, preferentially produced by T_H17 lymphocytes, regulates CNS barrier function

Area of Science:

• Neuroimmunology
• Cytokine biology
• Blood-brain barrier research

Background:

• Multiple sclerosis (MS) involves neuroinflammation and compromised blood-brain barrier (BBB) integrity.
• The role of interleukin-26 (IL-26) in MS pathogenesis and BBB function remains unclear.
• T helper 17 (TH17) lymphocytes are implicated in MS, producing various cytokines.

Purpose of the Study:

• To investigate the role of IL-26 in neuroinflammatory processes in MS.
• To determine the effect of IL-26 on blood-brain barrier (BBB) integrity.
• To assess the therapeutic potential of IL-26 in an MS model.

Main Methods:

• IL-26 expression was quantified in MS patients' serum, CSF, T helper cell subsets, and brain tissue.
• In vitro studies assessed IL-26's effect on human and mouse BBB endothelial cells (ECs).
• Experimental autoimmune encephalomyelitis (EAE) mice were treated with IL-26 to evaluate disease severity, BBB leakage, and immune cell infiltration.

Main Results:

• IL-26 expression was upregulated in MS patients and found in T lymphocytes infiltrating MS brain lesions.
• IL-26 receptors (IL-10R2 and IL-20R1) were detected on BBB ECs.
• IL-26 enhanced BBB integrity in vitro and in vivo, reduced EAE disease severity, and modulated immune cell infiltration into the CNS, favoring Tregs.

Conclusions:

• IL-26, preferentially expressed by TH17 lymphocytes, promotes BBB integrity and exhibits protective effects in chronic EAE.
• These findings highlight the functional diversity of TH17-derived cytokines and suggest IL-26 as a potential therapeutic target for MS.
• IL-26's dual role in modulating immune responses and maintaining BBB integrity offers new insights into MS pathogenesis.