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Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis.

Rogier R, Koenders MI, Abdollahi-Roodsaz S - J Immunol Res (2015)

Bottom Line: However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors.However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood.A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.

View Article: PubMed Central - PubMed

Affiliation: Experimental Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands.

ABSTRACT
In autoimmune diseases, a disturbance of the balance between T helper 17 (Th17) and regulatory T cells (Tregs) is often observed. This disturbed balance is also the case in rheumatoid arthritis (RA). Genetic predisposition to RA confers the presence of several polymorphisms mainly regulating activation of T lymphocytes. However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors. Multiple studies have shown that commensal gut microbiota is of great influence on immune homeostasis and can trigger the development of autoimmune diseases by favoring induction of Th17 cells over Tregs. However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood. Here we review the current evidence supporting the involvement of commensal intestinal microbiota in rheumatoid arthritis, along with a potential role of Toll-like receptors (TLRs) in modulating the relevant Th cell responses to trigger autoimmunity. A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.

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Related in: MedlinePlus

Toll-like receptor (TLR) activation on antigen presenting cells (APCs) enhances the antigenic signal to T cells. TLR activation induces the upregulation of MHC II (1), costimulatory molecules such as CD80, CD86, and CD40 (2), and release of cytokines (3).
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fig2: Toll-like receptor (TLR) activation on antigen presenting cells (APCs) enhances the antigenic signal to T cells. TLR activation induces the upregulation of MHC II (1), costimulatory molecules such as CD80, CD86, and CD40 (2), and release of cytokines (3).

Mentions: Antigen presenting cells (APCs) such as DCs and macrophages are known to express TLRs, and activation of TLRs induces the upregulation of MHC class II molecules and thereby may substantially influence the strength of the antigenic signal to T cells in the “immunological synapse” [54] (Figure 2). Furthermore, activation of TLRs induces upregulation of costimulatory molecules such as CD80, CD86, and CD40, which provide the second signal for T cell activation (Figure 2). The third signal for T cell activation and differentiation, the cytokine environment, is dramatically affected by the type and the extent of TLR activation (Figure 2). For instance, activation of TLR4 and TLR9 is thought to skew T cell differentiation toward the Th1 phenotype through induction of IL-12 production by DCs, whereas TLR2 activation might induce a Th2-biased immune response through production of IL-10 and IL-13 [55–61]. TLR4-induced IL-23 contributes to the expansion and survival of Th17 cells [62]. In addition, conditioned medium from TLR4-stimulated DCs or PBMCs induces Th17 differentiation and IL-17 production, a process potentiated by TGFβ [63].


Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis.

Rogier R, Koenders MI, Abdollahi-Roodsaz S - J Immunol Res (2015)

Toll-like receptor (TLR) activation on antigen presenting cells (APCs) enhances the antigenic signal to T cells. TLR activation induces the upregulation of MHC II (1), costimulatory molecules such as CD80, CD86, and CD40 (2), and release of cytokines (3).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352938&req=5

fig2: Toll-like receptor (TLR) activation on antigen presenting cells (APCs) enhances the antigenic signal to T cells. TLR activation induces the upregulation of MHC II (1), costimulatory molecules such as CD80, CD86, and CD40 (2), and release of cytokines (3).
Mentions: Antigen presenting cells (APCs) such as DCs and macrophages are known to express TLRs, and activation of TLRs induces the upregulation of MHC class II molecules and thereby may substantially influence the strength of the antigenic signal to T cells in the “immunological synapse” [54] (Figure 2). Furthermore, activation of TLRs induces upregulation of costimulatory molecules such as CD80, CD86, and CD40, which provide the second signal for T cell activation (Figure 2). The third signal for T cell activation and differentiation, the cytokine environment, is dramatically affected by the type and the extent of TLR activation (Figure 2). For instance, activation of TLR4 and TLR9 is thought to skew T cell differentiation toward the Th1 phenotype through induction of IL-12 production by DCs, whereas TLR2 activation might induce a Th2-biased immune response through production of IL-10 and IL-13 [55–61]. TLR4-induced IL-23 contributes to the expansion and survival of Th17 cells [62]. In addition, conditioned medium from TLR4-stimulated DCs or PBMCs induces Th17 differentiation and IL-17 production, a process potentiated by TGFβ [63].

Bottom Line: However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors.However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood.A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.

View Article: PubMed Central - PubMed

Affiliation: Experimental Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands.

ABSTRACT
In autoimmune diseases, a disturbance of the balance between T helper 17 (Th17) and regulatory T cells (Tregs) is often observed. This disturbed balance is also the case in rheumatoid arthritis (RA). Genetic predisposition to RA confers the presence of several polymorphisms mainly regulating activation of T lymphocytes. However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors. Multiple studies have shown that commensal gut microbiota is of great influence on immune homeostasis and can trigger the development of autoimmune diseases by favoring induction of Th17 cells over Tregs. However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood. Here we review the current evidence supporting the involvement of commensal intestinal microbiota in rheumatoid arthritis, along with a potential role of Toll-like receptors (TLRs) in modulating the relevant Th cell responses to trigger autoimmunity. A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.

Show MeSH
Related in: MedlinePlus