1078-C 5 JUNE 2020 • VOL 368 ISSUE 6495 sciencemag.org SCIENCE
associated with mangrove verti-
cal development, beyond which
the ecosystem fails to keep up
with the change. Under pro-
jected rates of sea level rise, they
predict that a deficit between
accretion and sea level rise is
likely to commence in the next
30 years. —AMS
Science, this issue p. 1118;
see also p. 1050
IMMUNOLOGY
Innate immune cells
remember
Immunological memory is a phe-
nomenon by which immune cells
can quickly recognize an antigen
that the host has previously
encountered. Certain cells of the
innate immune system exhibit
memory-like responses know
as trained immunity. Rapid,
antigen-specific secondary
(anamnestic) responses were
long thought to be the domain of
B and T cells. However, Dai et al.
report that monocytes and mac-
rophages can acquire memory
specific for particular major
histocompatibility complex I
antigens using paired A-type
immunoglobulin-like receptors
(PIR-As) (see the Perspective by
Dominguez-Andrés and Netea).
This pathway contributes to
recognition and rejection of
allograft-transplanted tis-
sue from a donor of the same
species. Genetic depletion or
blockade of PIR-As in mice
diminished the rejection of
kidney and heart allografts.
This work, which expands
immunological memory to
include myeloid cells, points to
targets that may improve organ
transplantation outcomes in the
future. —STS
Science, this issue p. 1122;
see also p. 1052
MOLECULAR BIOLOGY
DNA barcodes in small
packages
Under adverse environmental
conditions, some microorgan-
isms form spores that provide
robust protection for genetic
material. Qian et al. developed a
system in which DNA barcodes
are encapsulated inside non-
germinating microbial spores
and can be dispersed on objects
or in the environment (see the
Perspective by Nivala). These
barcoded spores provide a
durable, specific marker that can
be read out quickly with simple
equipment. When applied to soil,
the spores can be transferred
to and from objects around
them, enabling tracking at
meter-scale resolution. On plant
leaves, the spores are not readily
transferred, and the authors
demonstrate a potential use for
tracking agricultural products.
—MAF
Science, this issue p. 1135;
see also p. 1058GENE EDITING
Enforced editing
Various autoimmune diseases
could potentially be treated
with regulatory T cells (Tregs),
but there are many hurdles
between this idea and clini-
cal execution. Honaker et al.
devised a gene-editing strategy
to enforce the expression of
FOXP3, the master Treg tran-
scription factor, in CD4+ T cells
isolated from human peripheral
blood, thereby overcoming the
limitations of Treg isolation and
expansion. The resulting stable
FOXP3 expression enabled a
suppressive phenotype in vitro,
and the edited cells were also
functional in both a xenogeneic
graft-versus-host disease model
and an experimental autoim-
mune encephalitis model. This
approach has the potential to
rapidly translate to clinical use.
—LP
Sci. Transl. Med. 12 , eaay6422 (2020).PHARMACOLOGY
More targeted endothelial
protection
The bioactive lipid S1P exerts
effects in diverse tissues.
Unbiased agonists of the S1P
receptor S1P 1 trigger a reduced
lymphocyte count, or lympho-
penia, a useful feature when
treating autoimmune diseases
but an undesirable side effect
when activating S1P 1 in other cell
types. Poirier et al. identified a
G protein–biased S1P 1 agonist,
SAR247799, which maintained
endothelial function and reduced
tissue damage caused by
ischemia-reperfusion injury in
two different animal models. The
characteristics of SAR247799
show that it is possible to
target S1P 1 in the endothelium
without compromising immune
responses. —WW
Sci. Signal. 12 , eaax8050 (2020).RESEARCH
Published by AAAS