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Toll like receptors in autoimmune inflammatory demyelination: relevance to Multiple Sclerosis
Author(s) -
Brien Kate O’,
Gran Bruno
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.668.6
Subject(s) - tlr5 , immunology , tlr9 , tlr4 , chemokine , cytokine , tlr2 , tlr3 , toll like receptor , tlr7 , receptor , medicine , inflammation , biology , immune system , innate immune system , biochemistry , gene expression , dna methylation , gene
Multiple Sclerosis is a demyelinating disease of the central nervous system. We aim to find mechanisms by which toll like receptors (TLRs) exacerbate or suppress CNS inflammatory demyelination. Both effects have been observed in an animal model of MS ‐ TLRs 2 and 9 in exacerbating disease, TLR4 in delaying onset and TLR3 in reducing severity. We studied the response of human monocyte derived dendritic cells (MDDCs) to TLR stimuli in terms of maturation and cytokine and chemokine production. The inflammatory chemokine MCP‐1 was unregulated by TLR stimuli poly(I:C) (TLR3) and lipopolysaccharide (LPS) (TLR4). The inflammatory cytokines IL‐6 and TNF‐α were unregulated by these two stimuli and also by Pam3CSK4 (TLR1/2) and HKLM (TLR2). The effects of TLRs on MDDCs in MS patients are in progress. We also determined which cytokines and chemokines are induced by TLR stimuli in murine splenocytes. MCP‐1 was unregulated by TLR stimuli ‐ Pam3CSK, HKLM, LPS, Flagellin (TLR5), follistatin‐like 1 (TLR6) and ssRNA40 (TLR7). The anti‐inflammatory cytokine IL‐10 was unregulated by the same stimuli and also by poly(I:C) and CpG ODN1826 (TLR9). TLR9 also induced increased production of IL12p70. All TLR stimuli also induced increased T cell proliferation. The production of cytokines in response to TLR stimuli may regulate autoimmune diseases and there is potential to aid immunotherapy by targeting these TLRs and the cytokines produced.