Page 669 - Veterinary Immunology, 10th Edition

VetBooks.ir The Aryl Hydrocarbon Receptor

The aryl hydrocarbon receptor (AhR) was originally identified as a
transcription factor in the liver where it controls cellular responses
to aromatic hydrocarbons such as dioxanes and bisphenols. It also

regulates the enzymes that metabolize xenobiotics such as
cytochrome p450. Its endogenous ligands include derivatives of
tryptophan, indoles, and lipoxins. Dietary tryptophan is
metabolized by lactobacilli to generate indole-3-aldehyde,

tryptamine, and indole, all of which are AhR ligands.
AhR plays an important role in regulating immune responses.
Thus it is expressed at high levels in antigen-presenting cells,
intraepithelial lymphocytes, Th17, and Treg cells. Ligand binding

to the AhR stimulates IL-23 production and Th17 differentiation.
IL-22 from these cells enhances production of anti-microbial
peptides. The development of ILC3 cells depends upon AhR
expression and activation. AhRs are essential for the formation of

intraepithelial lymphocytes, cryptopatches, and isolated lymphoid
follicles. Defective AhR signaling results in severe intestinal
inflammation and the development of allergies. Thus AhR
knockout mice mount enhanced Th2 responses and higher levels of

IgE and IgG1. Their dendritic cells express higher levels of CD86
and MHC class II molecules. AhR signaling negatively affects the
type I interferon response.
AhR ligands such as indoles and flavonoids are naturally found

in cruciferous vegetables (cabbage, cauliflower, lettuce). These act
through AhRs to maintain IELs and promote normal intestinal
lymphoid function. AhRs also play an important role in resistance
to Pseudomonas aeruginosa, Mycobacterium tuberculosis, Listeria,

Toxoplasma, Leishmania and Trypanosoma cruzi.

B Cell Functions

There is more immune activity in the intestine than in all other
lymphoid tissues combined. It has been estimated that more than

80% of the body's activated B cells are found in the intestine. Their
function is to defend against possible invasion by the microbiota.
Although the microbiota are separated by the inner mucus layer

and glycocalyx from direct contact with enterocytes, intestinal

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