We deleted hepcidin in cDCs by crossing
CD11cCremice withHampF/Fmice.HampDCD11c
mice exhibited a selective loss of hepcidin ex-
pression in cDCs (Fig. 3A and fig. S4A). DC
development and systemic iron inHampDCD11c
mice were comparable to controls (fig. S4, B
to D). Furthermore, lymphocyte, myeloid, and
granulocyte responses were similar inHampDCD11c
mice and controls during naïve conditions and
after administration of DSS (figs. S4, E and F,and S5, A to C). Global transcriptional profiling
also revealed minimal changes in cDC subsets
fromHampDCD11cmice relative to controls
(fig. S6). Thus, cDC-derived hepcidin does
not affect immune responses in these contexts.188 10 APRIL 2020•VOL 368 ISSUE 6487 sciencemag.org SCIENCE
Fig. 3. Dendritic cell–derived hepcidin acts
on ferroportin-expressing phagocytes to facili-
tate mucosal healing.(A) Hepcidin expression
was determined by qPCR in mice exposed to DSS
for 7 days. (BtoD) Mice were given DSS for
8 days, and recovery was monitored by weight
change (B), H&E staining of the distal colon
(C), and colon shortening (D). (E) Sort-purified
cells from the naïve mouse colon were analyzed
for Slc40a1 expression by qPCR. (FtoH) Mice
were given DSS for 7 days, and recovery was
monitored by weight change (F), H&E staining of
the distal colon (G), and colon shortening (H).
Data in (D) and (H) were analyzed by unpaired
two-tailed Studentttest. In (B) and (F), weights
at killing, normalized to starting weight, were
analyzed by unpaired two-tailed Studentttest.
Data in (A) to (D) are representative of at
least two independent experiments withn= 3 to
5 per group; data in (F) and (H) are pooled
from, and data in (G) are representative of,
three independent experiments withn=1
to 3 per group. Data are means ± SEM.
**P< 0.01. Scale bars, 200mm.
Fig. 4. Dendritic cell–derived hepcidin seques-
ters iron to shape the intestinal microbiota.
(AandB) Mice were exposed to DSS for 7 days.
Whole cecal tissues were analyzed for iron
levels by quantitative mass spectrometry imaging
(A), and iron levels were quantified in colon
lumen contents (B). (C) Fecal microbiota were
analyzed by 16SrRNA gene sequencing and
principal coordinates analysis. (D)Micewere
exposed to DSS for 7 days, and bacterial
colony-forming units (CFU) were quantified from
colon tissue homogenates. (EandF) Mice were
given DSS in drinking water for 7 days and
treated daily with either phosphate-buffered
saline (PBS) vehicle or DFO from day 0 through
day 11. DSS-induced disease and recovery were
monitored by weight loss (E) and H&E staining of
the distal colon (F). In (A), two independent
experiments withn= 1 to 5 per group were
performed; representative data are shown. Data
in (B) and (E) are pooled from two independent
experiments, each withn= 3 to 5 per group.
Data in (C) and (D) are representative of two
independent experiments withn= 5 per group.
In (B) and (D), groups were compared by
unpaired two-tailed Studentttest. In (C),Pvalue
was determined using a permutational multi-
variate ANOVA test. In (E), weights at killing,
normalized to starting weight, were analyzed by one-way ANOVA using Tukeymultiple comparisons. In (F), representative data are shown from two independent
experiments withn= 3 to 5 per group. Data are means ± SEM. Scale bars, 200mm. *P< 0.05, **P< 0.01.
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