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@ARTICLE{Michel:130957,
author = {C. Michel$^*$ and C. N. Miller and R. Küchler$^*$ and B.
Brors$^*$ and M. S. Anderson and B. Kyewski$^*$ and S.
Pinto$^*$},
title = {{R}evisiting the {R}oad {M}ap of {M}edullary {T}hymic
{E}pithelial {C}ell {D}ifferentiation.},
journal = {The journal of immunology},
volume = {199},
number = {10},
issn = {1550-6606},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {DKFZ-2017-06033},
pages = {3488 - 3503},
year = {2017},
abstract = {The basic two-step terminal differentiation model of the
medullary thymic epithelial cell (mTEC) lineage from
immature MHC class II (MHCII)(lo) to mature MHCII(hi) mTECs
has recently been extended to include a third stage, namely
the post-Aire MHCII(lo) subset as identified by
lineage-tracing models. However, a suitable surface marker
distinguishing the phenotypically overlapping pre- from the
post-Aire MHCII(lo) stage has been lacking. In this study,
we introduce the lectin Tetragonolobus purpureas agglutinin
(TPA) as a novel cell surface marker that allows for such
delineation. Based on our data, we derived the following
sequence of mTEC differentiation: TPA(lo)MHCII(lo) →
TPA(lo)MHCII(hi) → TPA(hi)MHCII(hi) → TPA(hi)MHCII(lo)
Surprisingly, in the steady-state postnatal thymus
TPA(lo)MHCII(lo) pre-Aire rather than terminally
differentiated post-Aire TPA(hi)MHCII(lo) mTECs were marked
for apoptosis at an exceptionally high rate of $∼70\%.$
Hence, only the minor cycling fraction of the MHCII(lo)
subset $(<20\%)$ potentially qualified as mTEC precursors.
FoxN1 expression inversely correlated with the fraction of
slow cycling and apoptotic cells within the four TPA
subsets. TPA also further subdivided human mTECs, although
with different subset distribution. Our revised road map
emphazises close parallels of terminal mTEC development with
that of skin, undergoing an alternative route of cell death,
namely cornification rather than apoptosis. The high rate of
apoptosis in pre-Aire MHCII(lo) mTECs points to a 'quality
control' step during early mTEC differentiation.},
cin = {D090 ; D090 / G200 / L101},
ddc = {610},
cid = {I:(DE-He78)D090-20160331 / I:(DE-He78)G200-20160331 /
I:(DE-He78)L101-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28993517},
doi = {10.4049/jimmunol.1700203},
url = {https://inrepo02.dkfz.de/record/130957},
}