A key role for IL‐7R in the generation of microenvironments required for thymic dendritic cells

Abstract

Interleukin-7 receptor (IL-7R) signaling is critical for multiple stages of T-cell development, but a role in the establishment of the mature thymic architecture needed for T-cell development and thymocyte selection has not been established. Crosstalk signals between developing thymocytes and thymic epithelial cell (TEC) precursors are critical for their differentiation into cortical TECs (cTECs) and medullary TECs (mTECs). Additionally, mTECs-derived factors have been implicated in the recruitment of thymic dendritic cells (DCs) and intrathymic DC development. We therefore examined corticomedullary structure and DC populations in the thymus of Il7r−/− mice. Analysis of TEC phenotype and spatial organization revealed a striking shift in the mTEC to cTEC ratio, accompanied by disorganized corticomedullary structure. Several of the thymic subsets known to have DC potential were nearly absent, accompanied by reductions in DC cell numbers. We also examined chemokine expression in the Il7r−/− thymus, and found a significant decrease in mTEC-derived CCR7 ligand expression, and high levels of cTEC-derived chemokines, including CCL25 and CXCL12. Although splenic DCs were similarly affected, bone marrow precursors capable of giving rise to DCs were unperturbed. Finally, bone marrow chimeras showed that there was no intrinsic need for IL-7R signaling in the development or recruitment of thymic DCs, but that the provision of WT progenitors enhanced reconstitution of thymic DCs from Il7r−/− progenitors. Our results are therefore supportive of a model in which Il7r-dependent cells are required to set up the microenvironments that allow accumulation of thymic DCs.

Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis

“…Moore et al. ( 85 ) set out to elucidate the mechanism of IL-7’s influence on DC biology. They examined the corticomedullary structure and DC populations in IL-7R - thymus, showing that a loss of IL-7R – dependent cells led to an inverted ratio of medullary thymic epithelial cells (mTECs) to cortical thymic epithelial cells (cTECs).…”

Endogenous retroviruses transcriptomes in response to four avian pathogenic microorganisms infection in chicken

“…The expression of ChERVs' neighboring immune-related genes including S1PR1, SLC39A10, TRAF6, VEGFC, IL7R, CAV1 and MET were signi cantly up-regulated after APEC infection ( Supplementary Table S7). These ChERVs' neighboring immune-related genes such as SLC39A10, TRAF6, and IL7R have been found to play an important role in host immune responses [27][28][29]. However, there is no further reports indicating that the function of these immune-related genes is related to ERVs.…”

Endogenous retroviruses transcriptomes in response to four avian pathogenic microorganisms infection in chicken

“…The expression of ChERVs' neighboring immune-related genes including S1PR1, SLC39A10, TRAF6, VEGFC, IL7R, CAV1 and MET were significantly up-regulated after APEC infection (Additional file 9: Table S7). These ChERVs' neighboring immune-related genes such as SLC39A10, TRAF6, and IL7R have been found to play an important role in host immune responses [35][36][37]. However, there is no further reports indicating that the function of these immune-related genes is related to ERVs.…”