ライフサイエンスコーパス: mTEC

1 mTEC are a heterogeneous population of cells that differ

2 mTEC expression of LTbetaR is essential for the developm

3 mTECs also express multiple transcription factors requir

4 mTECs regulate T cell tolerance by ectopically expressin

5 An additional mTEC subset produces the chemokine CCL21, thereby attrac

6 ted reciprocal link between DETC and Aire(+) mTEC maturation.

7 ure thymocytes are not essential for Aire(+) mTEC development, use of an inducible ZAP70 transgenic m

8 Despite this role, the mechanisms of Aire(+) mTEC development remain unclear, particularly those stag

9 apping OPG expression to a subset of Aire(+) mTEC, our data show how cis- and trans-acting mechanisms

10 reveals that distinct DC subsets and AIRE(+) mTECs contribute substantially to presentation of divers

11 Aire(-) mTEC progenitors into CD80(+)Aire(+) mTECs, and that transplantation of RANK-deficient thymic

12 80(lo), Aire(-) mTECs into CD80(hi), Aire(+) mTECs; responsiveness to RANKL; and sustained expression

13 hanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for C

14 at emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to alphabet

15 nally, although initial formation of Aire(+) mTECs depends upon RANK signaling, continued mTEC develo

16 In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independ

17 are essential for differentiation of AIRE(+) mTECs.

18 orally linked with the appearance of Aire(+) mTECs.

19 factor-7, maintained a stable pool of Aire(+)mTEC(high), with an improved TRA transcriptome despite a

20 rfered with the capacity of recipient Aire(+)mTEC(high) to sustain TRA diversity.

21 ertoire secondary to a decline in the Aire(+)mTEC(high) cell pool.

22 maturation of RANK-expressing CD80(-)Aire(-) mTEC progenitors into CD80(+)Aire(+) mTECs, and that tra

23 erminal differentiation of CD80(lo), Aire(-) mTECs into CD80(hi), Aire(+) mTECs; responsiveness to RA

24 ing medullary thymic epithelial cells (Aire1 mTEC) and a decrease in the diversity of Aire-dependent

25 lineage-tracing analysis indicated that all mTECs have a history of receiving a notch signal, consis

26 programs of epithelial differentiation among mTECs.

27 ion, maintenance of thymic architecture, and mTEC differentiation.

28 However, the mechanisms controlling cTEC and mTEC production from the common TEPC are not understood.

29 d medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage

30 ets that reside within both the mTEC(hi) and mTEC(lo) compartments and that represent direct targets

31 edullary thymic epithelial cells (mTEC), and mTEC development in turn requires signals from mature si

32 lish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development, and are thus

33 Thus, GILT expression in thymic APCs, and mTECs in particular, preferentially facilitates MHC clas

34 tively than adult TECs; 2) whereas cTECs and mTECs had similar turnover rates in young mice, the turn

35 both cortical and medullary TECs (cTECs and mTECs) proliferated more actively in females than males.

36 ic epithelial cells (TECs), termed cTECs and mTECs, respectively.

37 the relationship between Il7(YFP+) TECs and mTECs.

38 e interactions between CD4(+) thymocytes and mTECs critically prevent multiorgan autoimmunity.

39 ency of Il7(YFP+) TECs gradually declines as mTEC development unfolds, we explored the relationship b

40 I(lo) subset (<20%) potentially qualified as mTEC precursors.

41 sent self-antigens at least as frequently as mTECs.

42 -antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance.

43 fore, while protecting against autoimmunity, mTECs simultaneously limit the generation of tumor-speci

44 reveal an unappreciated cooperation between mTECs and CD8alpha(+) DCs for presentation of Aire-induc

45 ome (BAC)-transgenic mouse lines with biased mTEC(lo) or mTEC(hi) expression of model antigens.

46 pha transgene also rescues the UEA-1 binding mTEC subset even though K5 expression is not detectable

47 Both mTEC populations show high splicing entropy, potentially

48 Development of both mTEC subsets requires activation of the noncanonical NF-

49 oxN1 is required for the development of both mTECs and cTECs in thymic organogenesis, it is most impo

50 cells, with transcriptional features of both mTECs and dendritic cells, comprising four major sub-gro

51 CD70 on both mTECs and DCs contributed to Treg cell development as sh

52 r, model antigen expression predominantly by mTEC(lo) supports TCRalphabeta(+) CD8alphaalpha intraepi

53 presentation of endogenous self-antigens by mTECs.

54 en this autophagy substrate was expressed by mTECs in high amounts, endogenous presentation and indir

55 lineages and that expression of some TRAs by mTECs may reflect this activity.

56 Thus, expression of some TRAs by mTECs may represent coordinated gene expression that ref

57 f peripheral tissue-restricted Ags (TRAs) by mTECs remain poorly defined.

58 -25, while LTbetaR controls CD104(+)CCL21(+) mTEC(low) that are capable of IL-15-transpresentation fo

59 F-kappaB-mediated differentiation of CD80(+) mTECs.

60 ll, Il7(YFP+) TECs can generate some CD80(+) mTECs in a stepwise differentiation process via YFP(-)Ly

61 Gas2l2(-/-) mouse tracheal epithelial cell (mTEC) cultures and in X. laevis embryos treated with Gas

62 sed primary murine tracheal epithelial cell (mTEC) cultures to investigate antiviral and cytokine res

63 show that medullary thymic epithelial cell (mTEC) development involves hemopoietic cross-talk, and n

64 regulating medullary thymic epithelial cell (mTEC) development.

65 we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted

66 del of the medullary thymic epithelial cell (mTEC) lineage from immature MHC class II (MHCII)(lo) to

67 stimulate medullary thymic epithelial cell (mTEC) maturation are partially elucidated, the signals t

68 t contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3(+

69 (cTEC) and medullary thymic epithelial cell (mTEC) subsets take place.

70 at mature medullary thymic epithelial cells (mTEC(high)) expressing the autoimmune regulator are targ

71 in mature medullary thymic epithelial cells (mTEC(high)) partly controlled by the autoimmune regulato

72 Both medullary thymic epithelial cells (mTEC) and dendritic cells (DC) present tissue-restricted

73 olerance, medullary thymic epithelial cells (mTEC) collectively express most protein-coding genes, th

74 Medullary thymic epithelial cells (mTEC) contribute to the development of T cell tolerance

75 generate medullary thymic epithelial cells (mTEC) from their immature progenitors, we describe work

76 e thymus, medullary thymic epithelial cells (mTEC) regulate T cell tolerance via negative selection a

77 endent on medullary thymic epithelial cells (mTEC), and mTEC development in turn requires signals fro

78 n, namely medullary thymic epithelial cells (mTECs) and dendritic cells, whereas TRP1 expression was

79 d Aire(+) medullary thymic epithelial cells (mTECs) and on dendritic cells (DCs) in the thymic medull

80 in mouse medullary thymic epithelial cells (mTECs) and peripheral lymphoid stromal cells, which have

81 genes in medullary thymic epithelial cells (mTECs) and, consequently, negative selection of effector

82 Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the

83 role for medullary thymic epithelial cells (mTECs) during iNKT cell development in the mouse thymus.

84 xpressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both n

85 Medullary thymic epithelial cells (mTECs) eliminate self-reactive T cells by displaying a d

86 Medullary thymic epithelial cells (mTECs) express a broad spectrum of tissue- restricted se

87 relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exh

88 ed Ags by medullary thymic epithelial cells (mTECs) is associated with negative selection.

89 tation by thymic medullary epithelial cells (mTECs) is controlled predominantly by Aire at the transc

90 (TRAs) in medullary thymic epithelial cells (mTECs) is essential for the induction of self-tolerance

91 (TRAs) in medullary thymic epithelial cells (mTECs) is essential to safeguard self-tolerance.

92 APCs and medullary thymic epithelial cells (mTECs) on the conventional and Treg TCR repertoire, as w

93 Medullary thymic epithelial cells (mTECs) play a critical role in central immune tolerance

94 xpressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by exp

95 Medullary thymic epithelial cells (mTECs) play an essential role in establishing central to

96 Medullary thymic epithelial cells (mTECs) play an important role in T cell tolerance and pr

97 APCs and medullary thymic epithelial cells (mTECs) played nonoverlapping roles in shaping the T cell

98 (TRAs) by medullary thymic epithelial cells (mTECs) plays an essential role in T cell tolerance.

99 xpressing medullary thymic epithelial cells (mTECs) provide a spectrum of tissue-restricted Ags that,

100 elopment, medullary thymic epithelial cells (mTECs) provide appropriate instructive cues in the thymi

101 ated that medullary thymic epithelial cells (mTECs), a unique type of APC of stromal origin, possess

102 ressed by medullary thymic epithelial cells (mTECs), has been less explored.

103 In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an es

104 s involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tiss

105 epends on medullary thymic epithelial cells (mTECs), whose development, in turn, requires signals fro

106 murine and human medullary epithelial cells (mTECs), with citrullinated proteins detected in murine m

107 xpressing medullary thymic epithelial cells (mTECs), without affecting its expression in the beta-cel

108 cells and medullary thymic epithelial cells (mTECs)--are yet to be developed.

109 (AIRE)(+) medullary thymic epithelial cells (mTECs).

110 dependent medullary thymic epithelial cells (mTECs).

111 genome in medullary thymic epithelial cells (mTECs).

112 xpressing medullary thymic epithelial cells (mTECs).

113 d Aire-deficient medullary epithelial cells (mTECs).

114 In conclusion, mTEC specialization controls intrathymic iNKT cell devel

115 mTECs depends upon RANK signaling, continued mTEC development to the involucrin(+) stage maps to acti

116 , their impact on the mechanisms controlling mTEC homeostasis is poorly understood, as are the proces

117 tem transit-amplifying population of cycling mTECs that preceded Aire expression.

118 in nude mice, and associated with defective mTEC-mediated elimination of thymocytes in a T cell rece

119 To further define mTEC development and medullary epithelial lineage relati

120 esignated as ID-TEC mice for insulin-deleted mTEC) developed diabetes spontaneously around 3 weeks af

121 developmental programs active in developing mTECs-may be equally plausible.

122 a key property of terminally differentiated mTECs.

123 alized property of terminally differentiated mTECs.

124 nalysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft c

125 A distinct mTEC subset binds UEA-1 and expresses K8, but not K5 or

126 oxA, FoxJ1, Hnf4, Sox8, and SpiB-in distinct mTEC subtypes.

127 We find three distinct mTEC(low) subsets distinguished by surface, intracellula

128 During mTEC maturation, rates of global transcript mis-initiati

129 Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTC

130 nts to a "quality control" step during early mTEC differentiation.

131 transcriptome of medullary thymic epithelia (mTECs) to produce a stroma decorated with peripheral sel

132 tly transfected medullary thymus epithelial (mTEC(+)) and B-cell (M12)-derived cell lines.

133 , the extent of medullary thymic epithelium (mTEC) heterogeneity, and the mechanisms that mediate the

134 n interactive public interface for exploring mTEC transcriptomic diversity.

135 ls gives rise to Aire- and Ccl21a-expressing mTEC subsets.

136 -displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expr

137 lopment of normal numbers of AIRE-expressing mTECs in the complete absence of SP thymocytes.

138 Thus, therapies to deplete Aire-expressing mTECs represent an attractive strategy to increase the p

139 RANKL) in the development of Aire-expressing mTECs.

140 gnaling pathway selectively in K5-expressing mTECs and 2) the K5-expressing subset either contains im

141 nate immune cell system drives initial fetal mTEC development via expression of RANKL, but not CD40L.

142 with each TRA being expressed in only a few mTECs.

143 Finally, mTECs regulate both iNKT-mediated activation of thymic d

144 or of NF-kappaB (RANK), which is central for mTEC differentiation, deficiency of p53 in TECs altered

145 and CD40, which are otherwise necessary for mTEC development, but is not sufficient to overcome the

146 we highlight recent work showing a role for mTEC-mediated thymic selection in maintaining maternal-f

147 This requirement for mTECs correlates with their expression of genes required

148 the TCR repertoire in a manner distinct from mTEC presentation.

149 enitor TEC and that, once specified, further mTEC development is NOTCH independent.

150 Furthermore, mTEC development is abnormal in iNKT cell-deficient mice

151 Further, TSPAN8(+) and GP2(+) mTEC were randomly dispersed within thymic medullary isl

152 and Hnf4gamma in TECs ablated entero-hepato mTECs and downregulated numerous gut- and liver-associat

153 Entero-hepato mTECs conserved their thymic identity yet accessed wide

154 ire, and tissue-restricted genes in CD80(hi) mTECs.

155 MHC class II (MHCII)(lo) to mature MHCII(hi) mTECs has recently been extended to include a third stag

156 Prss16 and segregates from CD80(+)CD40(high) mTECs expressing Tnfrsf11a, Ctss, and Aire.

157 lear bodies upon cotransfection and in human mTECs in situ.

158 Here, we show that subsets of human mTECs expressing a particular TRA coexpress distinct set

159 TPA also further subdivided human mTECs, although with different subset distribution.

160 e confirmed RBFOX to be present with AIRE in mTEC nuclei.

161 e needed to overcome TRAF3-imposed arrest in mTEC development mediated by inhibition of nonclassical

162 rWSN NS1 R38A replication is attenuated in mTEC cultures; however, viral antigen is detected predom

163 A decline in mTEC(high) cell pool size, which purges individual tissu

164 ing fetal stages, consistent with defects in mTEC specification and progenitor expansion.

165 , p53cKO mice presented premature defects in mTEC-dependent regulatory T-cell differentiation and thy

166 CD40-CD40L results in profound deficiency in mTEC development comparable to that observed in the abse

167 (m) and cortical TEC, further elaborated in mTEC, and completed in mature mTEC expressing the autoim

168 Comprehensive assessment of SF expression in mTEC identified a small set of nonpromiscuously expresse

169 of impaired thymic ectopic OVA expression in mTEC(high) cells.

170 inally, we show that whereas the increase in mTEC availability in OPG-deficient (Tnfrsf11b(-/-)) mice

171 olecular components and pathways involved in mTEC differentiation in general and in promiscuous gene

172 e strongly associated with H3K27me3 marks in mTEC.

173 d an absence of brain-specific microexons in mTEC.

174 consistent with notch signaling occurring in mTEC progenitors.

175 dence for a stepwise involvement of TNFRs in mTEC development, with CD40 upregulation induced by init

176 The failure to properly express CII in mTECs of Lta(-/-) and Ltbr(-/-) mice leads to overt auto

177 opic expression of type II collagen (CII) in mTECs and the corresponding central tolerance to CII are

178 /-) mice results in a profound deficiency in mTECs.

179 us, although it modulates gene expression in mTECs and in addition affects the size of the medullary

180 Our findings characterize TRA expression in mTECs as a coordinated process that might involve local

181 Aire-dependent control of Il7 expression in mTECs regulated the size of thymic IL-17A(+)Vgamma6(+)Vd

182 further that depletion of Ins2 expression in mTECs was sufficient to break central tolerance and indu

183 nduces tissue-specific antigen expression in mTECs, affected the TCR repertoire in a manner distinct

184 signaling and facilitates AIRE expression in mTECs.

185 l of control of Aire-activated expression in mTECs.

186 rence for short-3'UTR transcript isoforms in mTECs, a feature preceding Aire's expression and correla

187 ment of enhancer-associated histone marks in mTECs and also has characteristics of being an NF-kappaB

188 found that humans also lacked alpha-MyHC in mTECs and had high frequencies of alpha-MyHC-specific T

189 mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mT

190 ressed in the thymic stroma, specifically in mTECs.

191 itial and terminal differentiation stages in mTECs.

192 otherwise tissue-specific antigens (TSAs) in mTECs, and here we highlight recent work showing a role

193 Cs are highly heterogeneous; each individual mTEC expresses a limited spectrum of TRAs, and the frequ

194 saying chromatin accessibility in individual mTECs, we uncovered signatures of lineage-defining trans

195 imarily cytoplasmic localization in infected mTEC cultures.

196 p3(+) thymocyte lineages, in which an intact mTEC compartment is a prerequisite for Foxp3(+) nTreg ce

197 nstrates that the emergence of involucrin(+) mTECs critically depends upon the presence of mature sin

198 rmal equivalent, for the culture of isolated mTECs.

199 en by a K5 promoter restores the K5(+)K14(+) mTEC subset in IKKalpha(-/-) mice.

200 xpressed genes were confined to the CD80(lo) mTEC subset and preferentially included AIRE-independent

201 high rate of apoptosis in pre-Aire MHCII(lo) mTECs points to a "quality control" step during early mT

202 ly differentiated post-Aire TPA(hi)MHCII(lo) mTECs were marked for apoptosis at an exceptionally high

203 r with passing thymocytes, while maintaining mTEC identity.

204 elaborated in mTEC, and completed in mature mTEC expressing the autoimmune regulator gene (Aire).

205 ive differentiation stages within the mature mTEC subset and, in vitro, interconverted along this seq

206 y architecture and fewer functionally mature mTECs under steady-state conditions.

207 gulator (Aire), which is expressed in mature mTECs.

208 ed with activation of the p53 gene in mature mTECs.

209 pithelial lymphocyte development; meanwhile, mTEC(hi)-restricted expression preferentially induces T(

210 ptor activator for NF-kappaB ligand-mediated mTEC development.

211 ms operate independently of LTbetaR-mediated mTEC development and organization.

212 hat a functional compromise of the medullary mTEC(high) compartment may link alloimmunity to the deve

213 e to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors.

214 oter-driven somatic epithelial cells (mostly mTECs and possibly some adult epithelial stem cells) was

215 Remarkably, in mouse mTEC, Aire expression alone positively regulates 3980 ti

216 the thymus medulla by operating on multiple mTEC targets.

217 th citrullinated proteins detected in murine mTECs.

218 tories, stages and subtypes, including novel mTEC subsets, such as chemokine-expressing and ciliated

219 s study, we have investigated the control of mTEC homeostasis and examined how this process impacts t

220 n of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during

221 ll TECs resulted in widespread expression of mTEC progenitor markers and profound defects in TEC diff

222 We propose a branching model of mTEC development wherein a heterogeneous pool of transit

223 mpose important constraints for any model of mTEC differentiation and function.

224 tional heterogeneity allowed partitioning of mTEC into 15 reproducible subpopulations representing di

225 Cytokine pretreatment of mTEC cultures and Vero cells suggest that rWSN NS1 R38A

226 They also suggest a stepwise process of mTEC development, in which RANK is a master player in co

227 edulla to support the balanced production of mTEC-dependent Foxp3(+) Treg.

228 p53 controls specific and broad programs of mTEC differentiation.

229 TRAF3 plays a central role in regulation of mTEC development by imposing requirements for SP T cells

230 results identify Sin as a novel regulator of mTEC development and T cell tolerance, and suggest that

231 urnover, differentiation, and replacement of mTEC populations in the adult thymus.

232 ollectively, these data provide a roadmap of mTEC development and demonstrate the power of combinator

233 r data, we derived the following sequence of mTEC differentiation: TPA(lo)MHCII(lo) --> TPA(lo)MHCII(

234 ch self-antigen is expressed only in 1-3% of mTECs).

235 pathway, have an almost complete absence of mTECs, with resulting autoimmune pathology.

236 tore iNKT cell development in the absence of mTECs.

237 as a pathway important in the development of mTECs, because mice lacking RelB, NIK, or IKKalpha, crit

238 findings suggest that the differentiation of mTECs can involve some of the developmental programs use

239 y, Sin deficiency inhibited the expansion of mTECs in response to in vivo administration of keratinoc

240 -dimensional model preserves key features of mTECs: proliferation and terminal differentiation of CD8

241 mited spectrum of TRAs, and the frequency of mTECs that express any individual TRA is quite low (>0.4

242 iven the recently described heterogeneity of mTECs and DCs, it is unclear whether the antigen acquisi

243 it is most important for the maintenance of mTECs in the postnatal thymus, which are in turn necessa

244 that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis fact

245 rget genes was induced in only a minority of mTECs, independently of DNA-methylation patterns, as sma

246 ters activated in concert in a proportion of mTECs.

247 n patterns, each present in only a subset of mTECs.

248 urnover rates in young mice, the turnover of mTECs was more rapid than that of cTECs in adults; and 3

249 of the unusual features of Aire's impact on mTEC transcription, providing molecular insight into tol

250 One mTEC subset expresses keratin 5 (K5) and K14, but fails

251 -restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (

252 ansgenic mouse lines with biased mTEC(lo) or mTEC(hi) expression of model antigens.

253 red whole-genome gene signatures of purified mTEC subsets from TEC-specific Hipk2 knockout mice with

254 how multiple hemopoietic cell types regulate mTEC development through differential provision of RANKL

255 hat occur post-Aire expression and represent mTEC terminal differentiation.

256 To resolve mTEC diversity and whether promiscuous gene expression (

257 DC subset cDC2 efficiently acquires secreted mTEC-derived TRAs for cross-presentation on MHC-I.

258 mparison of the transcriptomes of 174 single mTEC indicates that genes induced by Aire expression are

259 we sequenced transcriptomes of 6,894 single mTEC, enriching for 1,795 rare cells expressing either o

260 How this process is regulated in single mTECs and is coordinated at the population level, such t

261 Our data suggest that single mTECs shift through distinct gene pools, thus scanning a

262 sion in individual and small pools of sorted mTECs show that mTECs are highly heterogeneous; each ind

263 tudy, in mouse thymus, we analyze late-stage mTEC development in relation to the timing and requireme

264 ily disrupts the integrity of medullary TEC (mTEC) niche, a defect that spreads to the adult cortical

265 fically expressed in Aire(+) medullary TECs (mTECs) induced efficient deletion via direct presentatio

266 more severe deterioration in medullary TECs (mTECs) than in cortical TECs (cTECs).

267 d map emphazises close parallels of terminal mTEC development with that of skin, undergoing an altern

268 In this study, we show that mTEC development is severely impaired and autoimmune man

269 within the thymus medulla, and it shows that mTEC homeostasis is not a rate-limiting step in intrathy

270 In summary, our data suggest that mTEC subsets may have a function in directing distinct m

271 We find that mTECs and DCs cooperate extensively to induce tolerance,

272 We report here that mTECs from adult mice are mitotically active, implying c

273 These data indicate that mTECs exert a cell-autonomous role in central T cell tol

274 al and small pools of sorted mTECs show that mTECs are highly heterogeneous; each individual mTEC exp

275 Our data suggest that mTECs and DCs form dedicated niches in the thymic medull

276 The mTEC population in adult thymus expresses transcription

277 RANK(+) subsets that reside within both the mTEC(hi) and mTEC(lo) compartments and that represent di

278 naling is required to specify and expand the mTEC lineage.

279 l (Treg) development, and alterations in the mTEC compartment can lead to tolerance breakdown and aut

280 r, on average, in individual TEC than in the mTEC population.

281 rmacological means increased the size of the mTEC compartment, enhanced negative selection and functi

282 l mimicking the developmental biology of the mTEC lineage has hampered the molecular analysis of the

283 for notch signaling in specification of the mTEC lineage.

284 have defined several basic properties of the mTEC population that refine our understanding of these c

285 s altered multiple functional modules of the mTEC transcriptome, including tissue-restricted antigen

286 own that gene-expression patterns within the mTEC compartment are heterogenous and include multiple d

287 quently controlling proliferation within the mTEC compartment.

288 sion and terminal differentiation within the mTEC lineage are temporally separable events that are co

289 Importantly, this mTEC heterogeneity enables the thymus to differentially

290 Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of

291 inism but is 'bookmarked' and stable through mTEC divisions, which ensures more effective presentatio

292 Thus, mTEC development can occur in the absence of cross-talk

293 node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peri

294 Even when TRA expression is restricted to mTECs, DCs still present self-antigens at least as frequ

295 eas TRP1 expression was restricted solely to mTECs.

296 tracing and recovery from transient in vivo mTEC ablation with single-cell RNA-sequencing in Mus mus

297 Whether mTEC subsets induce distinct autoreactive T cell fates r

298 Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expr

299 CD4(+)3(-) cells are closely associated with mTECs in adult thymus, and in fetal thymus their appeara

300 ell development is medullary dependent, with mTECs fostering the generation of Foxp3(-)CD25(+) nTreg