Correction: Established Thymic Epithelial Progenitor/Stem Cell-Like Cell Lines Differentiate into Mature Thymic Epithelial Cells and Support T Cell Development

ABSTRACT PRSS16 is a serine protease expressed exclusively in cortical thymic epithelial cells (cTEC) of the thymus, suggesting that it plays a role in the processing of peptide antigens during the positive selection of T cells. Moreover, the human PRSS16 gene is encoded in a region near the class I major histocompatibility complex (MHC) that has been linked to type 1 diabetes mellitus susceptibility. The mouse orthologue Prss16 is conserved in genetic structure, sequence, and pattern of expression. To study the role of Prss16 in thymic development, we generated a deletion mutant of Prss16 and characterized T-lymphocyte populations and MHC class II expression on cortical thymic epithelial cells. Prss16-deficient mice develop normally, are fertile, and show normal thymic morphology, cellularity, and anatomy. The total numbers and frequencies of thymocytes and splenic T-cell populations did not differ from those of wild-type controls. Surface expression of MHC class II on cTEC was also similar in homozygous mutant and wild-type animals, and invariant chain degradation was not impaired by deletion of Prss16. These findings suggest that Prss16 is not required for quantitatively normal T-cell development.

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Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells

Blood ◽

10.1182/blood-2006-10-049767 ◽

2007 ◽

Vol 109 (9) ◽

pp. 3803-3811 ◽

Cited By ~ 124

Author(s):

Simona W. Rossi ◽

Lukas T. Jeker ◽

Tomoo Ueno ◽

Sachiyo Kuse ◽

Marcel P. Keller ◽

...

Keyword(s):

T Cell ◽

Growth Factor ◽

Epithelial Cells ◽

Stromal Cells ◽

Keratinocyte Growth Factor ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells ◽

Thymic Stromal Cells ◽

Architectural Organization

Abstract The systemic administration of keratinocyte growth factor (KGF) enhances T-cell lymphopoiesis in normal mice and mice that received a bone marrow transplant. KGF exerts protection to thymic stromal cells from cytoablative conditioning and graft-versus-host disease–induced injury. However, little is known regarding KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here, we report that KGF induces in vivo a transient expansion of both mature and immature thymic epithelial cells (TECs) and promotes the differentiation of the latter type of cells. The increased TEC numbers return within 2 weeks to normal values and the microenvironment displays a normal architectural organization. Stromal changes initiate an expansion of immature thymocytes and permit regular T-cell development at an increased rate and for an extended period of time. KGF signaling in TECs activates both the p53 and NF-κB pathways and results in the transcription of several target genes necessary for TEC function and T-cell development, including bone morphogenetic protein 2 (BMP2), BMP4, Wnt5b, and Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis.

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mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development

The Journal of Immunology ◽

10.4049/jimmunol.1502698 ◽

2016 ◽

Vol 197 (1) ◽

pp. 141-150 ◽

Cited By ~ 8

Author(s):

Hong-Xia Wang ◽

Joyce S. Cheng ◽

Shuai Chu ◽

Yu-Rong Qiu ◽

Xiao-Ping Zhong

Keyword(s):

T Cell ◽

Epithelial Cells ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells

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Osteoprotegerin-Mediated Homeostasis of Rank+ Thymic Epithelial Cells Does Not Limit Foxp3+ Regulatory T Cell Development

The Journal of Immunology ◽

10.4049/jimmunol.1501226 ◽

2015 ◽

Vol 195 (6) ◽

pp. 2675-2682 ◽

Cited By ~ 23

Author(s):

Nicholas I. McCarthy ◽

Jennifer E. Cowan ◽

Kyoko Nakamura ◽

Andrea Bacon ◽

Song Baik ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

Regulatory T Cell ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells

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LAMTOR2 Is Dispensable for T Cell Receptor-Mediated Signaling of Thymocytes but Controls Medullary Thymic Epithelial Cells

Blood ◽

10.1182/blood-2018-99-119645 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1122-1122

Author(s):

Lina Wendeler ◽

Lukas A Huber ◽

Christoph Klein ◽

Daniel Kotlarz

Keyword(s):

T Cell ◽

Epithelial Cells ◽

Conflicts Of Interest ◽

Critical Role ◽

T Cell Development ◽

Cell Development ◽

Conditional Knockout ◽

Poly I:C ◽

Thymic Epithelial Cells

Abstract Human LAMTOR2 deficiency is characterized by severe congenital neutropenia, growth failure, partial albinism, as well as B and T cell deficiencies (Bohn et al., Nat Med 2007). To determine the role of the endosomal adaptor LAMTOR2 in T cell development and homeostasis we used conditional knockout mouse models. Mx1-Cre-driven knockout of Lamtor2 resulted in reduction of thymus weight and total thymocyte numbers. Immunophenotyping revealed an impaired T cell development characterized by a partial block at the double negative CD4-CD8- T cell precursor stage after 7 and 21 days of poly I:C injection that induced deletion of the Lamtor2 gene. Since Mx1-Cre-driven knockout does not allow a discrimination between T cell intrinsic and extrinsic effects, we next generated pre-TCRα-iCre conditional knockout mice. In contrast to Mx1-Cre-Lamtor2fl/fl mice, mice with T cell-specific knockout of Lamtor2 showed normal frequencies of total thymocytes and T cell progenitor subsets. Furthermore, LAMTOR2-deficient thymocytes exhibited normal TCR signaling (p-ERK, p-LAT, p-LCK, p-PLCγ, Nur77) and internalization of TCRβ upon stimulation with anti-CD3ε +/- anti-CD28, indicating that LAMTOR2 in T cells is dispensable for thymocyte development. To assess whether T cell developmental defects in Mx1-Cre-Lamtor2fl/fl mice are caused by a dysfunctional thymic epithelium, we analyzed thymic epithelial cells (TECs) after 4 days of poly I:C injection by flow cytometry and detected a reduced ratio of CD45-EpCAM+UEA-1+Ly51- medullary TECs (mTECs) to CD45-EpCAM+UEA-1-Ly51+ cortical TECs in LAMTOR2-deficient mice. Further studies are underway to determine the role of LAMTOR2 in mTECs. Taken together, our findings show that LAMTOR2 is not required for TCR-mediated signaling but plays a critical role in controlling mTEC homeostasis. Disclosures No relevant conflicts of interest to declare.

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