Disease relevance of Il7r

• Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Ralpha signals [1].
• Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma [2].
• Expression of IL-7Ralpha was lost from all CD8+ T cells, including EBV epitope-specific populations, during acute IM [3].
• Analysis of gene-targeted mice and patients with severe combined immunodeficiency due to mutations of the alpha chain of the interleukin-7 receptor (IL-7Ralpha) has shown important differences between mice and humans in the role played by IL-7 in lymphoid development [4].
• These mice exhibited a significantly greater weight loss after total body irradiation compared with wild type, IL-7R alpha(+/+), mice [5].

High impact information on Il7r

• Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice [6].
• Mice lacking functional IL-7 or IL-7R alpha genes are severely deficient in developing thymocytes, T cells, and B cells [6].
• Here, we show that enforced expression of the bcl-2 gene in T-lymphoid cells (by crossing in the Emu-bcl-2 transgene) in IL-7R alpha-deficient mice results in a significant restoration of thymic positive selection and T cell numbers and function [6].
• D-J joining occurs normally in immature B lymphocytes from mice lacking the alpha-chain of the interleukin-7 receptor (IL-7Ralpha) [7].
• Bax deficiency partially corrects interleukin-7 receptor alpha deficiency [8].

Biological context of Il7r

• From these data, we conclude that commitment and/or differentiation to the NK1(+) natural T cell lineage requires signal transduction through the gammac, and once committed, their expansion requires signals relayed through the IL-7Ralpha [9].
• To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Ralpha Y449XXM motif in mice by knock-in mutagenesis (IL-7Ralpha(449F)) [1].
• Furthermore, in contrast to IL-7Ralpha-/- mice, FL-/- x IL-7Ralpha-/- mice also lack mature B cells and detectable committed B cell progenitors during fetal development [10].
• Gene inactivation of IL-7, IL-7R, and IL-2Rgamma resulted in severe impairment of B and T lymphopoiesis in mice [11].
• Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells [12].

Anatomical context of Il7r

• In contrast, NK1(+) T cells develop in IL-7Ralpha-deficient mice in the thymus, and they are present in the liver and in the spleen [9].
• Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis [10].
• To explore the role of IL-7/IL-7R system in gammadelta T- and NK-cell development, we have generated and analyzed IL-7R-deficient mice. gammadelta T cells were absent from skin, gut, liver, and spleen in the deficient mice [11].
• Interleukin-7 (IL-7) receptor alpha chain-deficient (IL-7R alpha-/-) mice have severely depleted lymphocyte populations and thymocyte development is arrested at the double-negative (DN) stage [13].
• IL-7 receptor alpha+ CD3(-) cells in the embryonic intestine induces the organizing center of Peyer's patches [14].

Associations of Il7r with chemical compounds

• Treatment of IL-7Ralpha-/- precursor T cells with the specific histone deacetylase inhibitor trichostatin A released the block of TCR-gamma gene rearrangement [15].

Physical interactions of Il7r

• Interleukin (IL)-7 interactions with its cognate receptor complex (IL-7Ralpha coupled to the common cytokine receptor gamma chain, gammac) play a dominant role in early thymopoiesis [16].
• Proliferation of a factor-dependent pre-B cell line (NAG8/7) in response to either TSLP or IL-7 was inhibited by anti-IL-7R alpha mAbs, suggesting that the functional TSLP receptor complex uses IL-7R alpha [17].

Regulatory relationships of Il7r

• This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DN cells, increased DN apoptosis, and decreased DN cell number [12].
• Promoter and chromatin crosslinking analyses suggest that PU.1 directly regulates transcription of the IL-7Ralpha gene [18].
• The absence of contraction correlated with decreased early inflammation and interferon-gamma production and an increased fraction of CD8(+) T cells expressing the interleukin 7 receptor at the peak of the response [19].
• The rare DPhic-Kit- blast cells that thus are salvaged for positive selection by expressing a self-major histocompatibility complex selectable TCRalpha/beta up-regulate IL-7R, but not c-Kit, and are the principal progenitors on the c-Kit- pathway; this c-Kit-IL-7R+ pathway is mainly CD4 lineage committed [20].

Other interactions of Il7r

• Intestinal IL-7Ralpha+ cells are lymphoid in morphology but CD3(-) and functional in both nu/nu and Rag2-/- mice [14].
• Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development [9].
• In contrast, no VCAM-1+ spots were detected in the embryonic nor neonatal il7ralpha-/- mice, suggesting that IL-7Ralpha signal is involved in the early phase of PP anlage formation [21].
• Furthermore, CXCL13 was found to be sufficient to mediate CD4+ CD3- IL-7R alpha hi cell recruitment in vivo to an ectopic site [22].
• In addition to the appearance of VCAM1+ spots, the clustering of IL-7Ralpha+ cells was absent in the jak3-/- mouse, though IL-7Ralpha+ cells are found to scatter over the intestine [21].

Analytical, diagnostic and therapeutic context of Il7r

• Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR) [2].
• Whole-mount in situ hybridization revealed the presence of interleukin-7 receptor-alpha spots in NF-kappaB2(-/-) mice, indicating no defect in PP organogenesis of NF-kappaB2(-/-) mice in principle [23].
• Examination of cytokine receptor expression by these thymocytes revealed a significant inhibition in the expression of the transcript for the IL-7 receptor alpha-chain (IL-7Ralpha), and these results were confirmed by flow cytometry [24].
• Here, we created PP-null mice by treating them with monoclonal anti-IL-7 receptor alpha chain (IL-7 R alpha) antibody during gestation and then immunized with antigen-encapsulated poly-lactic acid (PLA) microspheres [25].

References