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| Identifier |
000355065 |
| Title |
Ο ρόλος του TLR9 και της IL21 στην παθογένεια του συστηματικού ερυθηματώδους λύκου |
| Alternative Title |
The role of IL21 and TLR9 in the pathogenesis of systemic lupus erythematosus |
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Author
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Μουτάφη, Μαρία
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Thesis advisor
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Μπούμπας, Δημήτριος
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| Abstract |
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with multiple
clinical manifestations and unclear etiology. Decades of clinical research and animal studies have
indicated that both the innate and the adaptive immune system are involved in the pathogenesis
of SLE. The main characteristic of the disease is the T cell induced– B cell mediated
autoantibody production, against nuclear autoantigens. In this study, the contribution of the
intracellular toll- like receptor 9 (TLR9) that recognizes dsDNA and the recently discovered
interleukin 21 (IL21) is assessed in the disease pathogenesis. Genetic studies have associated
polymorphisms of these two factors with susceptibility to SLE development. In addition IL21
overproduction and TLR9 activation are implicated in enhanced differentiation of naïve B cells
and antibody responses, which correlate with SLE pathogenesis.
Here, it is shown that IL21 in combination with TLR9 stimulation promote the robust
differentiation of patient naïve B cells into plasma cells and induce the expression of CD86, a costimulatory
molecule that is related to antigen presenting capacity. The increased numbers of
plasma cells that occurred in the presence of IL21 and TLR9 agonist may reflect their
contribution to the aberrant function of B cells and the great numbers of auto- antibodies detected
in SLE patients. In addition, the increase in the expression of CD86 may indicate the enhanced
ability of B cells to activate naïve T cells. The effect of TLR9 stimulation was assessed on the
antigen presenting capacity of monocytes, which also have increased TLR9 expression in SLE,
with no significant results. In addition, TLR9 was found not to be expressed in monocyte derived
dendritic cells from SLE patients, as in healthy controls.
Presumably, the overproduction of IL21 and the enhanced TLR9 activation may act
synergistically in the pathogenesis of SLE by inducing the differentiation of naïve B cells into
plasma cells and enhancing B cell antigen presenting capacity. The accelerated plasma cell
differentiation may be related to the augmented production of autoantibodies, a common
hallmark of SLE. In addition, the enhanced capacity of B cells to present antigens may account
for the aberrant activation of naïve T cells in this autoimmune disease.
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| Physical description |
48 σ. : πιν. ; 30 εκ. |
| Language |
Greek, English, English |
| Subject |
Autoimmune Diseases |
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Lupus Erythematosus, Systemic |
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Αυτοάνοσα νοσήματα |
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Λύκος ερυθηματώδης, Συστηματικός |
| Issue date |
2008-12-15 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Notes |
Πρόγραμμα μεταπτυχιακών σπουδών: "Κυτταρική και γενετική αιτιολογία, διαγνωστική και θεραπευτική των ασθενειών του ανθρώπου" |
| Views |
186 |
Ο ρόλος του TLR9 και της IL21 στην παθογένεια του συστηματικού ερυθηματώδους λύκου
