Cutting Edge: Thymocyte-Independent and Thymocyte-Dependent Phases of Epithelial Patterning in the Fetal Thymus

Klug, David B.; Carter, Carla; Gimenez-Conti, Irma; Richie, Ellen R.

doi:10.4049/jimmunol.169.6.2842

Cited by 181 publications

(182 citation statements)

References 29 publications

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“…As shown in Figure 2a-c and in agreement with the literature (Klug et al, 1998), we observed prominent expression of K5 by medullary TE and a small subset of cortical TE in WT thymus, with the majority of the cortical TE expressing a K8 ϩ K5 Ϫ phenotype. We found K8 expression to be more widespread among medullary TE than has been previously reported (Klug et al, 1998(Klug et al, , 2002 and observed that most of the medullary TE was K5 ϩ K8 ϩ . As described previously (Klug et al, 1998), K14 expression was more restricted to medullary TE in the WT thymus when compared with K5; few cortical TE were K8 ϩ K14 ϩ , and the corticomedullary boundary of K14 expression was more distinct than that of K5 ( Fig.…”

Section: Patterns Of Keratin Expression By Te Are Altered In the Lckfsupporting

confidence: 53%

“…The basis for differences in K8 expression by medullary TE reported here and elsewhere (Klug et al, 1998(Klug et al, , 2002 is not obvious and may reflect the use of different fluorochomes (FITC vs. Alexa 488) or differences in instrumentation. Furthermore, because shifts in fluorescence color (green ϩ red 3 yellow) are very dependent on the relative intensity of the fluorescence signals involved, these spectral shifts may not accurately reflect the true extent of colocalization.…”

Section: Discussionmentioning

confidence: 60%

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FGFR2IIIb signaling regulates thymic epithelial differentiation

Dooley

Erickson

LaRochelle

et al. 2007

Developmental Dynamics

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Heterogeneous epithelial populations comprising the thymic environment influence early and late stages of T-cell development. The processes that regulate the differentiation of thymic epithelium and that are responsible for this heterogeneity are not well understood, although mesenchymal/epithelial interactions are clearly involved. Here, we show that targeted expression by thymocytes of an fibroblast growth factor receptor-2IIIb (FGFR2IIIb) ligand, FGF10, profoundly alters the differentiation and function of thymic epithelium (TE). Reconstitution of irradiated lckFGF10 mice with normal bone marrow restores normal thymic organization and function, while wild-type mice reconstituted with lckFGF10 bone marrow recapitulates some of the thymic alterations seen in lckFGF10 mice. We also demonstrate that interference with FGFR2IIIb signaling in the thymus with a soluble FGFR2IIIb dominant-negative fusion protein leads to precocious reductions in thymic size and cellularity that resemble age-related thymic involution. These findings indicate that TE compartments are dynamically maintained and that FGF signals are involved in this process. Developmental Dynamics 236:3459 -3471, 2007.

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Section: Patterns Of Keratin Expression By Te Are Altered In the Lckfsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 60%

FGFR2IIIb signaling regulates thymic epithelial differentiation

Dooley

Erickson

LaRochelle

et al. 2007

Developmental Dynamics

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show abstract

“…On a per-cell basis, CII expression was again reduced in Ltbr Ϫ/Ϫ mTECs relative to WT with GAPDH as internal control (data not shown). Furthermore, because K14 is specifically and constitutively expressed in the majority of mTECs (5,20). K14 was used as an internal control in real-time PCR, CII expression remained reduced in Ltbr Ϫ/Ϫ mTECs relative to WT (Fig.…”

Section: Thymic Expression Of CII Is Controlled By Ltmentioning

confidence: 99%

Lymphotoxin Pathway-Directed, Autoimmune Regulator-Independent Central Tolerance to Arthritogenic Collagen

Chin

Zhu

Christiansen

et al. 2006

The Journal of Immunology

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Ectopic expression of peripherally restricted Ags by medullary thymic epithelial cells (mTECs) is associated with negative selection. Autoimmune regulator (AIRE) is considered to be the master regulator of these Ags. We show in this study that the ectopic expression of type II collagen (CII) in mTECs and the corresponding central tolerance to CII are AIRE independent but lymphotoxin dependent. The failure to properly express CII in mTECs of Lta−/− and Ltbr−/− mice leads to overt autoimmunity to CII and exquisite susceptibility to arthritis. These findings define the existence of additional pathways of ectopic peripheral Ag expression, parallel to and independent of AIRE, which may cover an extended spectrum of peripheral Ags in the thymus.

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“…The early TECs generated during embryogenesis contain bipotent progenitor thymic epithelial cells (pTECs) that are capable of generating both cTECs and mTECs [2,3]. It is acknowledged that thymocyte development differentially affects cTEC development [4][5][6] and mTEC development [7,8]. However, how pTECs branch into cTECs and mTECs and what regulates their developmental pathways are not fully understood.…”

Section: Cortical Thymic Epithelial Cells (Ctecs) and Medullary Thymimentioning

confidence: 99%

CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells

Ohigashi

Takahama

2014

Eur J Immunol

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Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs),The shaping of T-cell repertoire that is immunocompetent (i.e. useful for self-defense) and self-tolerant (i.e. harmless to the body) is crucial for the development and maintenance of the immune system. Thymic epithelial cells (TECs), which are the major component of the thymic microenvironments, are essential for the generation and repertoire formation of T cells. The thymic cortex, which induces early T-cell development and the positive selection of functionally competent T cells, is characterized by a subset of TECs termed cortical thymic epithelial cells (cTECs), whereas the thymic medulla, which establishes self-tolerance in T cells by the negative selection of self-reactive T cells and the generation of regulatory T cells, is formed by another subset of TECs termed medullary thymic epithelial cells (mTECs). TECs are derived from the endodermal epithelium of the third pharyngeal pouch, and the transcription factor Foxn1 is required Correspondence: Prof. Yousuke Takahama e-mail: takahama@genome.tokushima-u.ac.jp for their generation [1]. The early TECs generated during embryogenesis contain bipotent progenitor thymic epithelial cells (pTECs) that are capable of generating both cTECs and mTECs [2,3]. It is acknowledged that thymocyte development differentially affects cTEC development [4][5][6] and mTEC development [7,8]. However, how pTECs branch into cTECs and mTECs and what regulates their developmental pathways are not fully understood.Several molecular markers that characterize cTECs and mTECs have been identified. For example, cTECs predominantly express keratin 8 (K8), CD205 (DEC205), and CD249 (Ly51), whereas mTECs highly express keratin 5 (K5), CD80, and molecules that bind to the lectin Ulex europaeus agglutinin 1 (UEA1) [9][10][11]. In addition, mTECs, including immature mTECs, strongly express the tight junction molecules claudin-3 and claudin-4 [12]. Molecules that define pTECs are less well known, although it was suggested that pTECs express Plet1 (MTS24) and doubly express K5 and K8 [9,13]. cTECs and mTECs have further been characterized by their expression of functional molecules. DLL4 and IL-7, whichwww.eji-journal.eu Eur. J. Immunol. 2014. 44: 2872-2875 HIGHLIGHTS 2873are important for the induction of early T-cell development, as well as the thymoproteasome subunit β5t and the serine proteasome Prss16, which are critical for the positive selection of developing thymocytes, are highly expressed by cTECs rather than mTECs [10,11]. The cytokine receptor RANK and the nuclear protein Aire, which are pivotal for mTEC development and function in establishing self-tolerance in T cells, are predominantly detectable in mTECs rather than cTECs [10,11]. Chemokines, which essentially regulate the migration of developing thymocytes, are also unequally expressed between cTECs and mTECs; CCL25 and CXCL12 are more abundant in cTECs than mTECs, whereas CCL19, CCL21, and XCL1 are more highly detectable in mTECs than cTECs [...

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Cutting Edge: Thymocyte-Independent and Thymocyte-Dependent Phases of Epithelial Patterning in the Fetal Thymus

Cited by 181 publications

References 29 publications

FGFR2IIIb signaling regulates thymic epithelial differentiation

FGFR2IIIb signaling regulates thymic epithelial differentiation

Lymphotoxin Pathway-Directed, Autoimmune Regulator-Independent Central Tolerance to Arthritogenic Collagen

CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells

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