Limits...
Priming dendritic cells for th2 polarization: lessons learned from helminths and implications for metabolic disorders.

Hussaarts L, Yazdanbakhsh M, Guigas B - Front Immunol (2014)

Bottom Line: A common feature of helminth infections is the manifestation of a type 2 immune response, characterized by T helper 2 (Th2) cells that mediate anti-helminth immunity.The molecular mechanisms that govern Th2 responses are poorly understood, although it is clear that dendritic cells (DCs), which are the most efficient antigen-presenting cells in the immune system, play a central role.Finally, we discuss the implication of these findings in the context of metabolic disorders, as recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Center , Leiden , Netherlands.

ABSTRACT
Nearly one quarter of the world's population is infected with helminth parasites. A common feature of helminth infections is the manifestation of a type 2 immune response, characterized by T helper 2 (Th2) cells that mediate anti-helminth immunity. In addition, recent literature describes a close association between type 2 immune responses and wound repair, suggesting that a Th2 response may concurrently mediate repair of parasite-induced damage. The molecular mechanisms that govern Th2 responses are poorly understood, although it is clear that dendritic cells (DCs), which are the most efficient antigen-presenting cells in the immune system, play a central role. Here, we review the molecular mechanisms by which DCs polarize Th2 cells, examining both helminth antigens and helminth-mediated tissue damage as Th2-inducing triggers. Finally, we discuss the implication of these findings in the context of metabolic disorders, as recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.

No MeSH data available.


Related in: MedlinePlus

Putative effects of targeting DCs for Th2 polarization on adipose tissue inflammation and insulin sensitivity. Adipose tissues of obese patients and high-fat diet-fed mice are characterized by the accumulation of pro-inflammatory immune cells, like Th1 cells and M1 macrophages, which mediate tissue-specific insulin resistance through secretion of pro-inflammatory cytokines like IFN-γ and TNF-α. By contrast, M2 macrophages that secrete IL-10 protect against insulin resistance via multiple routes. For instance, IL-10 can act directly on adipocytes to potentiate insulin signaling, inhibit Th1 cells and M1 macrophages, and induce regulatory T cells (Tregs), thereby promoting adipose tissue insulin sensitivity and glucose disposal. The maintenance of M2 macrophages in adipose tissue depends on the presence of IL-4, which can be derived from Th2 cells or eosinophils. Novel treatment strategies may therefore focus on therapeutic manipulation of adipose tissue dendritic cells for Th2 polarization.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4202775&req=5

Figure 2: Putative effects of targeting DCs for Th2 polarization on adipose tissue inflammation and insulin sensitivity. Adipose tissues of obese patients and high-fat diet-fed mice are characterized by the accumulation of pro-inflammatory immune cells, like Th1 cells and M1 macrophages, which mediate tissue-specific insulin resistance through secretion of pro-inflammatory cytokines like IFN-γ and TNF-α. By contrast, M2 macrophages that secrete IL-10 protect against insulin resistance via multiple routes. For instance, IL-10 can act directly on adipocytes to potentiate insulin signaling, inhibit Th1 cells and M1 macrophages, and induce regulatory T cells (Tregs), thereby promoting adipose tissue insulin sensitivity and glucose disposal. The maintenance of M2 macrophages in adipose tissue depends on the presence of IL-4, which can be derived from Th2 cells or eosinophils. Novel treatment strategies may therefore focus on therapeutic manipulation of adipose tissue dendritic cells for Th2 polarization.

Mentions: The ability of DCs to prime strong Th2 responses identifies these cells as an attractive target for therapeutic manipulation of the immune system in the context of metabolic disorders. DCs are widely studied as targets for development of vaccines and immunotherapies because of their capacity to regulate a wide array of T cell responses (106–108). It has been described that DCs accumulate in AT of obese patients and mice (109, 110), and therapeutic manipulation of DCs might also provide a new strategy for targeted treatment of metabolic disorders (Figure 2).


Priming dendritic cells for th2 polarization: lessons learned from helminths and implications for metabolic disorders.

Hussaarts L, Yazdanbakhsh M, Guigas B - Front Immunol (2014)

Putative effects of targeting DCs for Th2 polarization on adipose tissue inflammation and insulin sensitivity. Adipose tissues of obese patients and high-fat diet-fed mice are characterized by the accumulation of pro-inflammatory immune cells, like Th1 cells and M1 macrophages, which mediate tissue-specific insulin resistance through secretion of pro-inflammatory cytokines like IFN-γ and TNF-α. By contrast, M2 macrophages that secrete IL-10 protect against insulin resistance via multiple routes. For instance, IL-10 can act directly on adipocytes to potentiate insulin signaling, inhibit Th1 cells and M1 macrophages, and induce regulatory T cells (Tregs), thereby promoting adipose tissue insulin sensitivity and glucose disposal. The maintenance of M2 macrophages in adipose tissue depends on the presence of IL-4, which can be derived from Th2 cells or eosinophils. Novel treatment strategies may therefore focus on therapeutic manipulation of adipose tissue dendritic cells for Th2 polarization.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202775&req=5

Figure 2: Putative effects of targeting DCs for Th2 polarization on adipose tissue inflammation and insulin sensitivity. Adipose tissues of obese patients and high-fat diet-fed mice are characterized by the accumulation of pro-inflammatory immune cells, like Th1 cells and M1 macrophages, which mediate tissue-specific insulin resistance through secretion of pro-inflammatory cytokines like IFN-γ and TNF-α. By contrast, M2 macrophages that secrete IL-10 protect against insulin resistance via multiple routes. For instance, IL-10 can act directly on adipocytes to potentiate insulin signaling, inhibit Th1 cells and M1 macrophages, and induce regulatory T cells (Tregs), thereby promoting adipose tissue insulin sensitivity and glucose disposal. The maintenance of M2 macrophages in adipose tissue depends on the presence of IL-4, which can be derived from Th2 cells or eosinophils. Novel treatment strategies may therefore focus on therapeutic manipulation of adipose tissue dendritic cells for Th2 polarization.
Mentions: The ability of DCs to prime strong Th2 responses identifies these cells as an attractive target for therapeutic manipulation of the immune system in the context of metabolic disorders. DCs are widely studied as targets for development of vaccines and immunotherapies because of their capacity to regulate a wide array of T cell responses (106–108). It has been described that DCs accumulate in AT of obese patients and mice (109, 110), and therapeutic manipulation of DCs might also provide a new strategy for targeted treatment of metabolic disorders (Figure 2).

Bottom Line: A common feature of helminth infections is the manifestation of a type 2 immune response, characterized by T helper 2 (Th2) cells that mediate anti-helminth immunity.The molecular mechanisms that govern Th2 responses are poorly understood, although it is clear that dendritic cells (DCs), which are the most efficient antigen-presenting cells in the immune system, play a central role.Finally, we discuss the implication of these findings in the context of metabolic disorders, as recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Center , Leiden , Netherlands.

ABSTRACT
Nearly one quarter of the world's population is infected with helminth parasites. A common feature of helminth infections is the manifestation of a type 2 immune response, characterized by T helper 2 (Th2) cells that mediate anti-helminth immunity. In addition, recent literature describes a close association between type 2 immune responses and wound repair, suggesting that a Th2 response may concurrently mediate repair of parasite-induced damage. The molecular mechanisms that govern Th2 responses are poorly understood, although it is clear that dendritic cells (DCs), which are the most efficient antigen-presenting cells in the immune system, play a central role. Here, we review the molecular mechanisms by which DCs polarize Th2 cells, examining both helminth antigens and helminth-mediated tissue damage as Th2-inducing triggers. Finally, we discuss the implication of these findings in the context of metabolic disorders, as recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.

No MeSH data available.


Related in: MedlinePlus