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You AhR What You Eat:
Linking Diet and Immunity
Lora V. Hooper1,2,*
1The Howard Hughes Medical Institute
2Department of Immunology
The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
The aryl hydrocarbon receptor (AhR) is responsible for the toxic effects of environmental pollutants
such as dioxin, but little is known about its normal physiological functions. Li et al. (2011) now show
that specific dietary compounds present in cruciferous vegetables act through the AhR to promote
intestinal immune function, revealing AhR as a critical link between diet and immunity.
From childhood we learn that vegetables
are good for us, and most of us eat our
veggies without giving much thought
to the evidence behind this accepted
wisdom or to the mechanisms underlying
the purported health-boosting proper-
ties of a vegetable-rich diet. In this issue
of Cell, Li et al. (2011) uncover a link
between diet and immunity, showing
that specific dietary compounds found
at high levels in cruciferous vegetables
cabbage are essential for sustaining
intestinal immune function. Moreover,
they show that the molecular basis for
this link involves the aryl hydrocarbon
The AhR is best known for mediating
the toxic effects of dioxin, an environ-
mental pollutant that is found in industrial
byproducts and is a toxic contaminant
of some herbicides (Fernandez-Salguero
et al., 1995). AhR is part of the basic
helix-loop-helix/Per-Arnt-Sim (PAS) ho-
mology superfamily, whose members
play central roles in sensing environ-
mental factors such as oxygen and light.
In its inactive state, AhR resides in the
polycyclic aromatic hydrocarbons such
as dioxin, it translocates to the nucleus
where it heterodimerizes with the AhR
nuclear translocator (Arnt). The AhR-Arnt
battery of genes containing specific DNA
enhancer sequences known as AhR-
responsive elements (AhREs). Many AhR
target genes are xenobiotic-metabolizing
enzymes such as the cytochrome P450
family member Cyp1a1 (Ito et al., 2007).
Early studies of mice engineered to lack
AhR (Ahr?/?mice) suggested a role for
AhR in liver development (Fernandez-
Salguero et al., 1995). However, until
recently little else was known about the
physiological function of AhR or what
Li et al. provide fascinating new insight
into the physiological role of the AhR
by showing it to be essential for normal
work had revealed that AhR is expressed
by circulating proinflammatory T helper
17 (Th17) cells and that activation of AhR
by dioxin modulates the numbers of
Th17 cells in mouse models of autoim-
mune disease (Veldhoen et al., 2008;
Quintana et al., 2008). Expanding on
these prior findings, Li et al. quantified
AhR expression in a broad array of
tissues. Strikingly, they found that intrae-
pithelial lymphocytes (IELs) from intestine
and skin express especially high levels
of AhR. These unconventional T cells
inhabit the body’s epithelial barriers in
large numbers, intercalating between
contacts with their epithelial neighbors.
IELs have a number of unusual properties
relative to conventional T cells, including
a high proportion of cells bearing the gd
T cell receptor and a prevalence of
their positioning at epithelial surfaces,
IELs defend against assaults from the
environment. Essential functions include
promoting epithelial repair following injury
(Chen et al., 2002) and limiting epithelial
cell invasion by the vast populations of
Cell 147, October 28, 2011 ª2011 Elsevier Inc. 489