RESEARCH - Induction of interferon-alpa by immune complexes or liposomes in SLE and Sjogren's syndrome

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Arthritis Rheum. 2006 Jun;54(6):1917-27.

Induction of interferon-alpha by immune complexes or liposomes containing

systemic lupus erythematosus autoantigen- and Sjogren's syndrome

autoantigen-associated RNA.

Lovgren T, Eloranta ML, Kastner B, Wahren-Herlenius M, Alm GV, Ronnblom L.

Uppsala University, Uppsala, Sweden. Tanja.Lovgren@...

OBJECTIVE: To investigate the ability of systemic lupus erythematosus (SLE)

autoantigen- and Sjogren's syndrome (SS) autoantigen-associated U1 small

nuclear RNA (U1 snRNA) and hY1RNA to induce interferon-alpha (IFNalpha)

production. METHODS: In vitro-transcribed U1 snRNA or hY1RNA and lipofectin

were added to peripheral blood mononuclear cell (PBMC) cultures. Purified U1

snRNP particles and IgG from SLE patients (SLE-IgG) were added to cultures

of PBMCs, enriched monocytes, or natural interferon-producing cells (NIPCs);

the latter are also known as plasmacytoid dendritic cells (pDC). Cells were

double-stained for IFNalpha and either blood dendritic cell antigen 2

(NIPCs/pDC) or CD14 (monocytes) and then analyzed by flow cytometry. In some

experiments, RNase or inhibitors of Fc gamma receptor IIa (Fc gammaRIIa)

(specific antibodies), endocytosis (chloroquine, bafilomycin A), or

Toll-like receptors (TLRs; oligodeoxynucleotide 2088) were used. The

produced IFNalpha was measured by immunoassay. RESULTS: Lipofected U1 snRNA

and hY1RNA both induced IFNalpha production in monocytes, but not in

NIPC/pDC. In contrast, U1 snRNP combined with SLE-IgG induced IFNalpha

production only in NIPCs/pDC, and this response was decreased by RNase

treatment or inhibition of the Fc gammaRIIa, the endocytosis pathways, or

the TLRs.

CONCLUSION: Our finding that U1 snRNA and hY1RNA have IFNalpha-inducing

capacity indicates that immune complexes containing such RNA, for example U1

snRNP particles, can be at least partly responsible for the ongoing IFNalpha

production seen in SLE and SS. These results may help to explain the

molecular mechanisms behind the pathogenesis of these and other autoimmune

diseases in which autoantibodies to RNA-binding proteins occur.

PMID: 16729300

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6729300

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