Science - USA (2021-10-29)

548-A 29 OCTOBER 2021 • VOL 374 ISSUE 6567 science.org SCIENCE

duits for homeostatic myeloid and lymphoid
cell trafficking from the skull and vertebral
bone marrow ( 12 ).
These vascular highways allow B cells,
neutrophils, and monocytes to make their
way into the underlying dural tissue and
provide substantial contributions to its im-
mune repertoire, wholly independent of a
blood route ( 12 , 13 ). Such a pathway allows
for the delivery of a particular subset of im-
mune cells directly to CNS border tissues.
We hypothesized that the neuroimmune
surveillance afforded to the dural sinuses
ideally positions them to interpret CNS
dysfunction and relay this to adjacent bone
marrow, which can then deploy immune
cells in response to a variety of insults ( 6 ).
After neuroinflammatory injury induced
by experimental autoimmune encephalomy-
elitis (EAE), a mouse model of multiple scle-
rosis, elevated numbers of CNS bone mar-
row–derived cells were present in the dural
meninges and were no longer restricted to
the CNS borders ( 12 ). Monocytes infiltrating
the CNS were largely of local bone marrow
origin and frequently associated with bone
marrow channels. Similar patterns were ob-

served after optic nerve and spinal cord in-

juries, demonstrating a conserved ability of

CNS-associated bone marrow–derived cells

to infiltrate CNS tissue in the wake of varied

pathologies ( 12 ).

Not only does this local bone marrow

function as an immunological reservoir,

but the cells originating from this niche are

phenotypically distinct. Through scRNA-

seq of CNS-infiltrating cells following EAE

and spinal cord injury, we detected elevated

levels of pathogenic proinflammatory cy-

tokines and chemokines—which are impli-

cated in worsened pathology ( 14 )—in blood-

derived cells compared with their bone

marrow–derived counterparts ( 12 ). Cells

originating from local bone marrow likely

play distinct roles in CNS injury, shaped

by their specific ontogeny and interactions

with stromal niches during transit through

the dura ( 6 , 15 ).

COLLABORATIVE CARE

The complexities of neuroimmune inter-

actions are continuously being unraveled.

Our findings have uncovered an immuno-

logical orchestration that permits the CNS

to maintain its barriers and enable tight

regulation of cerebral function, while still

allowing antigenic sampling to recognize

CNS perturbations ( 6 ), and for the subse-

quent mobilization of tailor-made immune

cells from local bone marrow reservoirs

( 12 ). Through this clever compromise, the

CNS has pushed its immunity to its borders,

allowing uninterrupted neuronal function,

without completely sacrificing immunologi-

cal protection. j

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