18.4.5.5 Immunoregulation via the Aryl Hydrocarbon Receptor
The airways contain a number of cellular sensor systems that can monitor the content
of biogenic aerosols in inhaled air (Fig. 18.3). For example, many microbial pigments such as phenazines and naphthoquinones are Aryl Hydrocarbon Receptor
(AhR) agonists and have been shown to regulate inflammation and antibacterial
responses (Moura-Alves et al. 2014). However, even microbes with little direct AhR
agonist activity can trigger the AhR via their metabolites. Tryptophan can be
metabolised to produce AhR ligands that drive production of IL-22 by activated
cells that are abundant at mucosal surfaces such as DC, T cells, and innate lymphoid
cells (ILC). The protein IL-22 regulates reactions to microbial pathogens, especially
in respiratory and gut epithelial cells, and plays a major role in resistance to
colonization by fungi and by some bacterial species (Zelante et al. 2014). But
IL-22 also activates host indoleamine-2,3-dioxygenase 1, which generates further
tryptophan-derived AhR agonists. These drive production of TGF-β and Treg and so
contribute to setting up immunoregulation (Bessede et al. 2014; Quintana et al.
2008).
18.4.5.6 Contribution of Non-microbial Biogenic Particles
The cellular sensor systems in the airways that monitor the content of biogenic
aerosols will also detect molecules present in plant and pollen fragments. For
example, the PI3K/Akt/mTORC1 signalling system plays a role in inflammatory
pathways via NF-κB. Natural products from algae and higher plants (in addition to
products of bacteria and fungi) can inhibit the activities of these protein kinases, and
the overall effect is thought to be anti-inflammatory (Moore 2015).
Plant polyphenols can also exert anti-inflammatory effects via the Aryl hydrocarbon receptor (AhR). Thus, quercetin, resveratrol, and curcumin interfere with
metabolic degradation of the endogenous AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ). This increases FICZ levels and indirectly activates the AhR
(Mohammadi-Bardbori et al. 2012).
There is some evidence that miRNA from plants can trigger anti-inflammatory
effects via TLR3 (Cavalieri et al. 2016). These miRNA target dendritic cells and
reduce the ability of those cells to respond to inflammatory mediators and to drive T
cell responses. A preparation of plant miRNA injected intravenously was able to
attenuate Experimental Autoimmune Encephalomyelitis in a mouse model
(Cavalieri et al. 2016).
344
G. A. W. Rook
The airways contain a number of cellular sensor systems that can monitor the content
of biogenic aerosols in inhaled air (Fig. 18.3). For example, many microbial pigments such as phenazines and naphthoquinones are Aryl Hydrocarbon Receptor
(AhR) agonists and have been shown to regulate inflammation and antibacterial
responses (Moura-Alves et al. 2014). However, even microbes with little direct AhR
agonist activity can trigger the AhR via their metabolites. Tryptophan can be
metabolised to produce AhR ligands that drive production of IL-22 by activated
cells that are abundant at mucosal surfaces such as DC, T cells, and innate lymphoid
cells (ILC). The protein IL-22 regulates reactions to microbial pathogens, especially
in respiratory and gut epithelial cells, and plays a major role in resistance to
colonization by fungi and by some bacterial species (Zelante et al. 2014). But
IL-22 also activates host indoleamine-2,3-dioxygenase 1, which generates further
tryptophan-derived AhR agonists. These drive production of TGF-β and Treg and so
contribute to setting up immunoregulation (Bessede et al. 2014; Quintana et al.
2008).
18.4.5.6 Contribution of Non-microbial Biogenic Particles
The cellular sensor systems in the airways that monitor the content of biogenic
aerosols will also detect molecules present in plant and pollen fragments. For
example, the PI3K/Akt/mTORC1 signalling system plays a role in inflammatory
pathways via NF-κB. Natural products from algae and higher plants (in addition to
products of bacteria and fungi) can inhibit the activities of these protein kinases, and
the overall effect is thought to be anti-inflammatory (Moore 2015).
Plant polyphenols can also exert anti-inflammatory effects via the Aryl hydrocarbon receptor (AhR). Thus, quercetin, resveratrol, and curcumin interfere with
metabolic degradation of the endogenous AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ). This increases FICZ levels and indirectly activates the AhR
(Mohammadi-Bardbori et al. 2012).
There is some evidence that miRNA from plants can trigger anti-inflammatory
effects via TLR3 (Cavalieri et al. 2016). These miRNA target dendritic cells and
reduce the ability of those cells to respond to inflammatory mediators and to drive T
cell responses. A preparation of plant miRNA injected intravenously was able to
attenuate Experimental Autoimmune Encephalomyelitis in a mouse model
(Cavalieri et al. 2016).
344
G. A. W. Rook