Suppression of established experimental autoimmune encephalomyelitis and formation of meningeal lymphoid follicles by lymphotoxin beta receptor-Ig fusion protein.

Francesco Ria, Sandra Columba-Cabezas, Marilena Griguoli, Barbara Rosicarelli, Roberta Magliozzi, Barbara Serafini, Francesca Aloisi

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

56 Citazioni (Scopus)

Abstract

We have recently shown that de novo formation of lymphoid structures resembling B-cell follicles occurs in the inflamed central nervous system (CNS) meninges in a subset of patients with secondary progressive multiple sclerosis and in SJL mice with relapsing-remitting experimental autoimmune encephalomyelitis (EAE). Because lymphotoxin (LT) alpha(1)beta(2) is essential for lymphoid tissue organization, we used real-time PCR to examine LTbeta and LTbeta receptor (LTbetaR) gene expression in the CNS of SJL mice immunized with PLP 139-151 peptide. Moreover, we used the decoy receptor LTbetaR-immunoglobulin fusion protein to block the interaction of lymphotoxin (LT) alpha(1)beta(2) with the LTbeta receptor (LTbetaR) in mice with established EAE and evaluate the effect of systemic and local treatments with the fusion protein on disease progression, CNS lymphocytic infiltration and formation of meningeal B-cell follicles. The present findings indicate that both LTbeta and LTbetaR are upregulated at EAE onset and during subsequent relapses and that systemic and local blockade of the LT pathway with LTbetaR-Ig results in protracted and transient inhibition of EAE clinical signs, respectively. LTbetaR-Ig treatment also reduces T- and B-cell infiltration and prevents the induction of the chemokines CXCL10 and CXCL13 and the formation of organized ectopic follicles in the EAE-affected CNS. Targeting of molecules involved in lymphoid organogenesis could represent a valid strategy to inhibit CNS inflammation and formation of ectopic follicles, which may play a role in maintaining an abnormal, intrathecal humoral immune response in CNS autoimmune disease.
Lingua originaleEnglish
pagine (da-a)76-86
Numero di pagine11
RivistaJournal of Neuroimmunology
DOI
Stato di pubblicazionePubblicato - 2006

Keywords

  • EAE
  • Lymphotoxin

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