Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage

Self Cite

162

115

The functions of a chemokine CXC chemokine ligand (CXCL) 12/stromal cell-derived factor-1/pre-B cell growth stimulating factor and its physiologic receptor CXCR4 in T cell development are controversial. In this study, we have genetically further characterized their roles in fetal and adult T cell development using mutant and chimeric mice. In CXCL12−/− or CXCR4−/− embryos on a C57BL/6 background, accumulation of T cell progenitors in the outer mesenchymal layer of the thymus anlage during initial colonization of the fetal thymus was comparable with that seen in wild-type embryos. However, the expansion of CD3−CD4−CD8− triple-negative T cell precursors at the CD44−CD25+ and CD44−CD25− stages, and CD4+CD8+ double-positive thymocytes was affected during embryogenesis in these mutants. In radiation chimeras competitively repopulated with CXCR4−/− fetal liver cells, the reduction in donor-derived thymocytes compared with wild-type chimeras was much more severe than the reduction in donor-derived myeloid lineage cells in bone marrow. Triple negative CD44+CD25+ T cell precursors exhibited survival response to CXCL12 in the presence of stem cell factor as well as migratory response to CXCL12. Thus, it may be that CXCL12 and CXCR4 are involved in the expansion of T cell precursors in both fetal and adult thymus in vivo. Finally, enforced expression of bcl-2 did not rescue impaired T cell development in CXCR4−/− embryos or impaired reconstitution of CXCR4−/− thymocytes in competitively repopulated mice, suggesting that defects in T cell development caused by CXCR4 mutation are not caused by reduced expression of bcl-2.

Section: Impaired Expansion Of T Cell Precursors In the Thymus From Cmentioning

confidence: 62%

A Role of CXC Chemokine Ligand 12/Stromal Cell-Derived Factor-1/Pre-B Cell Growth Stimulating Factor and Its Receptor CXCR4 in Fetal and Adult T Cell Development in Vivo

Ara

Itoi

Kono

et al. 2003

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162

115

“…The migration of hematopoietic progenitors into the thymic primordium is initiated between E11 and E12, which corresponds temporally to the appearance of K8 ϩ K5 ϩ TEC clusters (20,21). This correlation suggests that interactions with differentiating thymocytes might induce K5 up-regulation in fetal TECs.…”

Section: Resultsmentioning

confidence: 92%

“…Itoi et al (20) reported that the thymic epithelium converts from a stratified bilayered epithelium at E11 to a clustered organization by E12 and a meshwork structure by E13. Our findings are consistent with this report and further show that K5 is up-regulated in a subset of TECs concomitant with or shortly after the thymic epithelium assumes a three-dimensional structure.…”

Section: It Is Not Yet Clear Whether the K8mentioning

confidence: 99%

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

Klug

Carter

Gimenez-Conti

et al. 2002

180

164

Thymic epithelial cells (TECs) in adult mice have been classified into distinct subsets based on keratin expression profiles. To explore the emergence of TEC subsets during ontogeny, we analyzed keratin 8 and keratin 5 expression at several stages of fetal development in normal C57BL/6J mice. In addition, thymic epithelial development and compartmentalization were explored in recombination-activating gene 2/common cytokine receptor γ-chain-deficient and Ikaros-null mice that sustain early and profound blocks in thymocyte differentiation. The results demonstrate that initial patterning of the thymic epithelial compartment as defined by differential keratin expression does not depend on inductive signals from hematopoietic cells. However, thymocyte-derived signals are required during late fetal stages for continued development and maintenance of TEC subsets in the neonate and adult.

“…Upon challenges, upregulation of Foxn1 was a common feature of thymus regeneration, but the timing of Foxn1 expression changed and the responding TEC subsets depended on the type of treatment. Whereas dexamethasone and recombinant human fibroblast growth factor 7 …”

mentioning

confidence: 99%

“…Separation of the common anlage coincides with the arrival of hematopoietic precursor cells from the bone marrow inside the thymus at embryonic day (E)12 (6,7). Although Foxn1-deficient mutants lack a functional thymus, a Foxn1-deficient thymic anlage nevertheless forms and migrates to its final mediastinal position above the heart (8).…”

mentioning

confidence: 99%

Foxn1 Protein Expression in the Developing, Aging, and Regenerating Thymus

Rodé

Martins

Küblbeck

et al. 2015

The forkhead box N1 (Foxn1) protein is the key regulator of thymic epithelial cell (TEC) development, yet how Foxn1 functions remains largely unknown. All mature TECs arise from Foxn1-expressing progenitors/immature TECs and it is widely assumed that TECs as a whole are defined by Foxn1 expression. However, data on the Foxn1 protein are virtually lacking. In this study, we developed novel tools to visualize Foxn1 protein expression at single-cell resolution. We generated Foxn1 knock-in mice expressing a C-terminal hemagglutinin-tagged Foxn1 protein, and a cytometry-grade monoclonal anti-Foxn1 Ab. We evaluated Foxn1 expression patterns in TEC subsets and its dynamics during normal thymus development, aging, injury, and regeneration. Upon challenges, upregulation of Foxn1 was a common feature of thymus regeneration, but the timing of Foxn1 expression changed and the responding TEC subsets depended on the type of treatment. Whereas dexamethasone and recombinant human fibroblast growth factor 7 promoted expansion of Foxn1+Ly51+CD80− TECs, castration led to expansion of Foxn1+Ly51−CD80+ TECs. Collectively, Foxn1 expression is highly heterogeneous in the normal thymus, with large fractions of Foxn1low or Foxn1− TECs accumulating with age. Furthermore, Foxn1 expression is responsive to perturbations.