Toll Receptors Modulate Allergic Responses
Toll Receptors Modulate Allergic Responses
Purpose of Review: The discovery of Toll-like receptors has generated much interest in understanding the impact of innate immunity on adaptive immune responses, including allergic diseases.
Recent Findings: Recent studies suggest that Toll-like receptor pathways may mediate interactions between dendritic cells, T lymphocytes and mast cells, thus modulating allergic immune responses. Toll-like receptor signaling triggers dendritic cell maturation, which primes naive T lymphocytes towards specific T helper cell types 1 and 2 immune responses. Although a T helper cell type 1/2 balance may be important in modulating allergic responses, T regulatory cells that suppress certain immune responses may be critical in immune regulation.
Summary: With the identification of different subsets of dendritic cells and the discovery of Toll-like receptors on T regulatory cells and mast cells, the manipulation of Toll-like receptor signaling may lead to novel therapeutic options in allergic diseases.
Allergic inflammation is mediated through adaptive immune responses characterized by antigen recognition in the context of MHC class II molecules on antigen-presenting cells (APCs) and presentation to T lymphocytes. The activation of T cells requires the expression of co-stimulatory molecules on APCs. Over a decade ago, Janeway postulated that co-stimulation is regulated by receptors with specificity for microbial products, thus linking the innate recognition of non-self with the induction of adaptive immunity.
Toll-like receptors (TLRs), homologues of Toll receptor in Drosophilia, induce innate responses, which occur early, within hours, and are likely candidates for regulating interactions with the adaptive immunity, which occurs within days. TLRs are germ-lined encoded receptors that recognize highly conserved microbial components known as the pathogen-associated molecular pattern and induce the expression of genes that control innate and adaptive immune responses. There are currently 10 recognized TLR family members, each characterized by the elicitation of differential signals, cellular location and ligand specificities, e.g. the cell wall component lipopolysaccharide of Gram-negative bacteria signals through TLR4, whereas peptidoglycan of Gram-positive bacteria signals through TLR2.
Although several previous reviews have focused on TLR signaling, the importance of TLRs in allergic diseases is less well understood. Studies analysing the influence of TLR stimulation on allergen-induced immune responses and TLR4 polymorphism-asthma associations have yielded heterogeneous results, suggesting that TLRs may modulate both pro and anti-allergic responses. A commonly held paradigm of such studies indicates that allergic diseases are predominantly associated with increased T helper (Th) cell type 2 and decreased Th1 cytokine secretion. In this review, we focus on the influence of TLR signaling on the function of inflammatory cells, specifically dendritic cells, T lymphocytes and mast cells in the modulation of allergic immune responses.
Purpose of Review: The discovery of Toll-like receptors has generated much interest in understanding the impact of innate immunity on adaptive immune responses, including allergic diseases.
Recent Findings: Recent studies suggest that Toll-like receptor pathways may mediate interactions between dendritic cells, T lymphocytes and mast cells, thus modulating allergic immune responses. Toll-like receptor signaling triggers dendritic cell maturation, which primes naive T lymphocytes towards specific T helper cell types 1 and 2 immune responses. Although a T helper cell type 1/2 balance may be important in modulating allergic responses, T regulatory cells that suppress certain immune responses may be critical in immune regulation.
Summary: With the identification of different subsets of dendritic cells and the discovery of Toll-like receptors on T regulatory cells and mast cells, the manipulation of Toll-like receptor signaling may lead to novel therapeutic options in allergic diseases.
Allergic inflammation is mediated through adaptive immune responses characterized by antigen recognition in the context of MHC class II molecules on antigen-presenting cells (APCs) and presentation to T lymphocytes. The activation of T cells requires the expression of co-stimulatory molecules on APCs. Over a decade ago, Janeway postulated that co-stimulation is regulated by receptors with specificity for microbial products, thus linking the innate recognition of non-self with the induction of adaptive immunity.
Toll-like receptors (TLRs), homologues of Toll receptor in Drosophilia, induce innate responses, which occur early, within hours, and are likely candidates for regulating interactions with the adaptive immunity, which occurs within days. TLRs are germ-lined encoded receptors that recognize highly conserved microbial components known as the pathogen-associated molecular pattern and induce the expression of genes that control innate and adaptive immune responses. There are currently 10 recognized TLR family members, each characterized by the elicitation of differential signals, cellular location and ligand specificities, e.g. the cell wall component lipopolysaccharide of Gram-negative bacteria signals through TLR4, whereas peptidoglycan of Gram-positive bacteria signals through TLR2.
Although several previous reviews have focused on TLR signaling, the importance of TLRs in allergic diseases is less well understood. Studies analysing the influence of TLR stimulation on allergen-induced immune responses and TLR4 polymorphism-asthma associations have yielded heterogeneous results, suggesting that TLRs may modulate both pro and anti-allergic responses. A commonly held paradigm of such studies indicates that allergic diseases are predominantly associated with increased T helper (Th) cell type 2 and decreased Th1 cytokine secretion. In this review, we focus on the influence of TLR signaling on the function of inflammatory cells, specifically dendritic cells, T lymphocytes and mast cells in the modulation of allergic immune responses.
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