Disease relevance of IL-7

• IL-2R gamma is a common gamma chain, gamma c, also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency [1].
• IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART [2].
• The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis [3].
• Surprisingly, serum osteocalcin levels, a biochemical marker of bone formation, suggested that the bone-sparing effects of IL-7 neutralization were due not only to inhibition of bone resorption, but also to stimulation of bone formation [4].
• Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events [5].

Psychiatry related information on IL-7

• Moreover IL-7, a newly cloned lymphokine, was found to support the growth and expansion of the human nature T cells [6].

High impact information on IL-7

• Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis [7].
• IL-2, IL-15, and IL-7 are cytokines that are critical for regulating lymphoid homeostasis [7].
• The control of CD4+ memory T cells is more mysterious, with roles reported for IL-7 and/or contact via the TCR [8].
• Their deaths are prevented in animals by IL-7 and contact with MHC [8].
• Some factors that control early lymphoid development are discussed, including IL-7 and the Ikaros transcription factors [9].

Chemical compound and disease context of IL-7

• Remarkably, the IL-12-conditioned CD8 T cells demonstrate increased sensitivity to IL-7 and IL-15, whereby they are rendered "fit" for homeostatic self-renewal as well as augmented CD4-dependent recall responses that are effective at controlling Salmonella infection in vivo [10].
• While Jak3 SCID patients possess mature peripheral B cells, we demonstrate that the Jak3 tyrosine kinase is also expressed in human pre-B cells and can be activated by the pre-B cell growth factor IL-7 [11].

Biological context of IL-7

• In agreement with representing a lymphoid primed progenitor, Lin-Sca-1+c-kit+CD34+Flt3+ cells display upregulated IL-7 receptor gene expression [12].
• IL-7 and IL-7 receptor functions are believed to result in lymphoid cell proliferation and cell maturation, implying signal transduction pathways directly involved in mitogenesis and elaboration of developmentally specific new gene programs [13].
• By contrast, for expression of more mature action potentials (tetrodotoxin-sensitive) one of the interleukins IL-5, IL-7 or IL-9 must be applied in association with transforming growth factor-alpha after pretreatment with basic fibroblast growth factor [14].
• The combination of IL-7 and interferons alpha/beta induces bcl-2 down-regulation and cell death by apoptosis [15].
• Treatment with the immunotoxin in conjunction with agents that activate virus expression without inducing cell division (IL-7 or the non-tumor-promoting phorbol ester prostratin) depleted the bulk of the latent reservoir and left uninfected cells able to respond to subsequent costimulation [16].

Anatomical context of IL-7

• In line with this, the frequency and proliferative capacity of IL-7-responsive B cell progenitors in fetal liver were severely decreased in vitro [17].
• EBF-deficient mice lack B cells that have rearranged their immunoglobulin D and JH gene segments, but contain B220+CD43+ progenitor cells that express germline mu and IL-7 receptor transcripts [18].
• These pre-BI cells fail to express the BSAP target gene CD19 and are capable of long-term proliferation in vitro in the presence of stromal cells and IL-7 [19].
• WECHE repressed BFU-E development from either mouse fetal liver or bone marrow progenitor cells but had no effect on colony formation induced by IL-3 or IL-7 [20].
• The common cytokine receptor gamma chain (gamma(c)) is an indispensable subunit for the formation of lymphoid-related cytokine receptors, including IL-7 and IL-15 receptors, that mediate nonredundant or critical signals for the differentiation of T and B cells and natural killer (NK) cells, respectively [21].

Associations of IL-7 with other chemical compounds

• We conclude that IL-7 is a pivotal upstream target through which estrogen regulates hematopoietic and immune functions that are critical for bone homeostasis [22].
• Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL-7, they remain responsive to this cytokine, which can reduce their sensitivity to imatinib [23].
• Tyrosine phosphorylation of several proteins (55 kd, 30 kd, and 24 kd) in HS-27a cells was rapidly increased after incubation with recombinant IL-7 [24].
• Furthermore, the extent of apoptosis inhibition by IL-7 in vitro quantitatively correlated with early cytoreduction as determined by the prednisone peripheral blood response on day 8 and cytoreduction in the marrow on day 15 (n = 87; P <.05) [25].
• In comparison to the control cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity [26].

Gene context of IL-7

• The interleukin-2 receptor (IL-2R) consists of three subunits: the IL-2R alpha, IL-2R beta, and IL-2R gamma chains, the last of which is also used in the receptors for IL-4, IL-7, and IL-9 [27].
• Thus, in young mice, Bax emerges as an essential protein in the death pathway induced by IL-7 deficiency [28].
• In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7) [29].
• Finally, these studies are consistent with the hypothesis that the molecular pathogenesis of X-SCID is due primarily to gamma(c)-mediated defects in the IL-7/IL-7R system [30].
• IL-7-mediated inhibition of TGF-beta signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family [3].

Analytical, diagnostic and therapeutic context of IL-7

• Among the cytokines sharing the gamma chain, at least IL-7 is essentially involved in early T cell development in the mouse organ culture system [31].
• Such proliferation is inhibited by the presence of both memory and naive CD4 T cells, is enhanced by 3-day thymectomy, is independent of IL-7, and requires a class II MHC-TCR interaction and a CD28-mediated signal [32].
• Thus, IL-7 may prove valuable for mobilizing pluripotent stem cells with long-term repopulating activity from the bone marrow to the peripheral blood for the purpose of gene modification and/or autologous or allogeneic stem cell transplantation [33].
• Here we demonstrate the expression of IL-7 mRNA in human intestinal mucosa by combined reverse transcription PCR and Southern blot hybridization [34].
• Immunohistochemistry and in situ hybridization confirm the presence of IL-7 in intestinal epithelial cells, especially in epithelial goblet cells [34].

References