Human MBP-specific T cells regulate IL-6 gene expression in astrocytes through cell–cell contacts and soluble factors

✍ Scribed by Marco Colombatti; Giuseppe Moretto; Marina Tommasi; Emma Fiorini; Ornella Poffe; Michaela Colombara; Raffaella Tanel; Giuseppe Tridente; Dunia Ramarli

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 141 KB
• Volume: 35
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.1087

✦ Synopsis

Abstract

One of the distinctive features of multiple sclerosis (MS) attacks is homing to the CNS of activated T cells able to orchestrate humoral and cell‐based events, resulting in immune‐mediated injury to myelin and oligodendrocytes. Of the complex interplay occurring between T cells and CNS constituents, we have examined some aspects of T‐cell interactions with astrocytes, the major components of the glial cells. Specifically, we focused on the ability of T cells to regulate the gene expression of interleukin‐6 (IL‐6) in astrocytes, based on previous evidence showing the involvement of this cytokine in CNS disorders. We found that T‐cell adhesion and T‐cell soluble factors induce IL‐6 gene expression in U251 astrocytes through distinct signaling pathways, respectively, resulting in the activation of NF‐κB and IRF‐1 transcription factors. In a search for effector molecules at the astrocyte surface, we found that α3β1 integrins play a role in NF‐κB activation induced by T‐cell contact, whereas interferon‐γ (IFN‐γ) receptors dominate in IRF‐1 induction brought about by T‐cell‐derived soluble factors. Similar phenomena were observed also in normal fetal astrocyte cultures. We therefore propose that through astrocyte induction, T cells may indirectly regulate the availability of a cytokine which is crucial in modulating fate and behavior of cell populations involved in the pathogenesis of MS inflammatory lesions. GLIA 35:224–233, 2001. © 2001 Wiley‐Liss, Inc.