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Effect of IL-7 on T cell regeneration. IL-7 regulates T cell homeostasis through three immune modulation pathways: thymic differentiation, peripheral expansion, and extrathymic differentiation. To regenerate peripheral T cells, IL-7 directs T cell differentiation and maturation in the thymus. As age-related decline in thymic function becomes apparent, IL-7 contributes to the maintenance of the T cell pool through the expansion of existing peripheral T cells. Extrathymic differentiation from CLP cells is possible but is only a minor pathway. In all three scenarios, IL-7 is known to have an important signaling effect.
Source publication
The age of an individual is an important, independent risk factor for many of the most common diseases afflicting modern societies. Interleukin-7 (IL-7) plays a central, critical role in the homeostasis of the immune system. Recent studies support a critical role for IL-7 in the maintenance of a vigorous healthspan. We describe the role of IL-7 and...
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B cell progenitors require paracrine signals such as interleukin-7 (IL-7) provided by bone marrow stromal cells for proliferation and survival. Yet, how B cells regulate access to these signals in vivo remains unclear. Here we show that proB and IL-7 ⁺ cells form a cell circuit wired by IL-7R signaling, which controls CXCR4 and focal adhesion kinas...
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine expressed in the skin, gut, lungs, and thymus. TSLP triggers dendritic cell-mediated T helper 2 inflammatory responses by formation of a ternary complex consisting of a heterodimer of interleukin-7 (IL-7) receptor α chain (IL-7Rα), TSLP, and the TSLP receptor chain (TSLPR)....
The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for de novo T cell generation in thymus and peripheral T cell homeostasis. In this study, we...
Background:
The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant...
Citations
... We also hypothesized that cytokines may have a greater chance of having cross-reactive epitopes of cSCSs because COVID-19 is characterized by a cytokine storm [106][107][108][109]. From the original list, we extracted proteins that had annotations of at least one of the following words: interleukin (IL), interferon (IF), tumor necrosis factor (TNF), or tumor growth factor (TGF). ...
Spike protein sequences in SARS-CoV-2 have been employed for vaccine epitopes, but many short constituent sequences (SCSs) in the spike protein are present in the human proteome, suggesting that some anti-spike antibodies induced by infection or vaccination may be autoantibodies against human proteins. To evaluate this possibility of “molecular mimicry” in silico and in vitro, we exhaustively identified common SCSs (cSCSs) found both in spike and human proteins bioinformatically. The commonality of SCSs between the two systems seemed to be coincidental, and only some cSCSs were likely to be relevant to potential self-epitopes based on three-dimensional information. Among three antibodies raised against cSCS-containing spike peptides, only the antibody against EPLDVL showed high affinity for the spike protein and reacted with an EPLDVL-containing peptide from the human unc-80 homolog protein. Western blot analysis revealed that this antibody also reacted with several human proteins expressed mainly in the small intestine, ovary, and stomach. Taken together, these results showed that most cSCSs are likely incapable of inducing autoantibodies but that at least EPLDVL functions as a self-epitope, suggesting a serious possibility of infection-induced or vaccine-induced autoantibodies in humans. High-risk cSCSs, including EPLDVL, should be excluded from vaccine epitopes to prevent potential autoimmune disorders.
... * Bernice Lo blo@sidra.org expression of cell cycle activation and anti-apoptotic genes [9,10]. IL-7Rα is a 459 amino acid protein encoded by the IL7R gene located on the short arm of chromosome 5 (5p13.2) [11,12]. ...
Purpose
The interleukin-7 receptor (IL-7R) is primarily expressed on lymphoid cells and plays a crucial role in the development, proliferation, and survival of T cells. Autosomal recessive mutations that disrupt IL-7Rα chain expression give rise to a severe combined immunodeficiency (SCID), which is characterized by lymphopenia and a T⁻B⁺NK⁺ phenotype. The objective here was to diagnose two siblings displaying the T⁻B⁺NK⁺ SCID phenotype as initial clinical genetic testing did not detect any variants in known SCID genes.
Methods
Whole genome sequencing (WGS) was utilized to identify potential variants causing the SCID phenotype. Splicing prediction tools were employed to assess the deleterious impact of the mutation. Polymerase Chain Reaction (PCR), Sanger sequencing, flow cytometry, and ELISA were then used to validate the pathogenicity of the detected mutation.
Results
We discovered a novel homozygous synonymous mutation in the IL7R gene. Our functional studies indicate that this variant is pathogenic, causing exon 6, which encodes the transmembrane domain, to be preferentially spliced out.
Conclusion
In this study, we identified a novel rare synonymous mutation causing a loss of IL-7Rα expression at the cellular membrane. This case demonstrates the value of reanalyzing genetic data based on the clinical phenotype and highlights the significance of functional studies in determining the pathogenicity of genetic variants.
... In addition to the inflammatory cytokines above, IL-7 and IL-15 levels were also determined in bone marrow. In this microenvironment, senescence affects multiple cells within the hematopoietic lineage, resulting in a gradual loss of self-renewal and differentiation capacity, both of which are important in immune function (61). Ikuta et al. (2022) also detected these interleukins in samples of bone marrow, lymph nodes, and thymus, and found different expressions in each tissue analyzed (62). ...
... This organ also undergoes changes throughout the aging and immunosenescence process, with a considerable reduction in the size of thymic structures, such as a decrease in the medullary zone, an increase in the cortical zone, and perivascular spaces. Despite these changes, the thymus still functions, however, with reduced capacity and effectiveness (61). In our histological analysis, we observed faster thymic involution in SAM-P8 mice. ...
Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism’s homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1β, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4⁺ and CD8⁺ T cell numbers were higher and lower, respectively, in SAM-P8 mice treated with RAPA, with the opposite observed in SAM-R1. Additionally, we found that the low dose of RAPA used did not trigger changes that could compromise the immune response of these mice and the administered dose may have contributed to changes in important lymphocyte populations in the adaptive immune response and the secretion of cytokines that directly collaborate with the maturation and proliferation of these cells.
... Among the genes proximate to these peaks is the IL7 locus, recognised for its involvement in growth and reproductive processes in pigs [38]. Remarkably, IL7 ′ s role in inflammatory responses [39], crucial for food digestion and nutrient absorption, has been documented in various pig populations, particularly in South African pig populations [40]. However, these responses may paradoxically dampen feed intake, consequently hindering growth rates. ...
There is still limited information on the genomic structure and genetic diversity of African pigs. Genetic diversity studies can contribute significantly to the genetic improvement and conservation of African pigs. This study presents a genetic diversity analysis and population structure of pig breeds in Ghana, with a focus on the Ashanti Dwarf pig (ADP), an indigenous pig breed of Ghana. A total of 167 pigs sampled in Ghana and populations consisting of Ashanti Dwarf pigs (n = 106), exotics (mostly European pigs) (n = 11), crosses (between indigenous and exotic breeds) (n = 44), and unknown breeds (nondescript) (n = 6) were genotyped using Porcine SNP60K BeadChip. Moderate heterozygosity levels, ranging from 0.28 for Ashanti Dwarf pigs to 0.31 for exotic pigs (mostly European pigs), were observed. Principal component analysis of the pig populations within Ghana resulted in two distinct clusters of pigs: (i) Northern and (ii) Southern regional clusters. The PCA based on breed also resulted in four clusters: (i) ADPs; (ii) exotics (iii) crossbreeds between ADP and exotics; (iv) unknown breed types. The PCA demonstrated that the clustering was influenced by genetics, geographical location, production systems, and practices. ADMIXTURE-based analysis also showed that the populations within Ghana are admixed. FST analysis revealed SNPs associated with QTLs for traits such as disease resilience and growth among ADP populations within the different regional and ecological zones of Ghana.
... Notably, B regs and plasma cells are recognized to favor oxidative phosphorylation. Therefore, high carbohydrate intake can save B-cell lymphogenesis due to IL-7 signaling defects [168]. Increased carbohydrate intake may also enhance the antibody response by supporting the glucose demand of long-lived plasma cells [169]. ...
Aging negatively affects B cell production, resulting in a decrease in B-1 and B-2 cells and impaired antibody responses. Age-related B cell subsets contribute to inflammation. Investigating age-related alterations in the B-cell pool and developing targeted therapies are crucial for combating autoimmune diseases in the elderly. Additionally, optimal nutrition, including carbohydrates, amino acids, vitamins, and especially lipids, play a vital role in supporting immune function and mitigating the age-related decline in B cell activity. Research on the influence of lipids on B cells shows promise for improving autoimmune diseases. Understanding the aging B-cell pool and considering nutritional interventions can inform strategies for promoting healthy aging and reducing the age-related disease burden.
... As a receptor of IL-7, CD127 plays an essential role in the development of T lymphocytes along with the maintenance of homeostasis in T cells and differentiation of memory T cells. 38 As previously reported, CD127, which acts as an excellent marker of Treg cells, is expressed at low levels on most of Treg cells. 39 Some of the strategies that cancer uses to evade the immune system are tolerance to peripheral T cells, including Treg and T cell anergy; fatigue; and aging, which impair T cellmediated immunity. ...
Background
In the era of immunotherapy, the immune function of patients with cancer has attracted increasingly more attention. The immune scoring system is an important supplement to the classical tumor staging and classification process. The immune system plays a controversial role in the development of cancer. Meanwhile, the prognostic significance of peripheral blood lymphocytes is still controversial. The present study aimed to assess the prognostic significance of peripheral blood lymphocytes in eight types of cancers.
Methods
We performed a retrospective analysis of 32731 patients with cancer hospitalized in Shanxi Cancer Hospital from January 2012 to December 2016. The percentages of CD3⁺, CD4⁺, CD8⁺, CD19⁺, CD56⁺, and CD127+ lymphocytes in the peripheral blood of all patients were examined using flow cytometry. The immune cell subsets of patients with cancer were classified into three groups using the K-means clustering method via the R language software. Differences in the overall survival rate were analyzed using the Kaplan–Meier method. The Cox regression model was utilized for univariate and multivariate analysis.
Results
The mean survival time of patients with liver cancer, rectal cancer, gastric cancer, breast cancer, esophageal cancer, colon cancer, ovarian cancer, and lymphoma was 30.25, 21.74, 37.67, 16.28, 21.62, 30.25, 31.43, and 34.27 months, respectively. The survival curves showed that the most prognostically beneficial immune state of the patients was when the expression of the immune cells in the peripheral blood was in equilibrium. Moreover, Cox proportional hazards regression model analysis revealed that the factors affecting the overall survival (OS) of patients with eight different kinds of cancer were not identical. However, CD19⁺ lymphocytes had the most significant impact on the prognosis of these patients.
Conclusions
Cancer occurrence and development were associated with the density of lymphocyte infiltration. Thus, immune homeostasis could be an effective indicator to evaluate prognosis and judge cancer treatment.
... IL-7 is a cytokine belonging to the IL-2 family that is synthesized by bone marrow stromal and epithelial cells (75). Its receptor is composed of two chains: IL-7R alpha (CD127) and gamma chain (CD132), which are expressed at high levels on quiescent T cells, except for CD4+CD25+ Tregs (76). ...
Immune thrombocytopenia (ITP) manifests as depleted platelet reserves, primarily due to the immune-mediated destruction of platelets. The pathogenesis of ITP is complex and involves dysregulation of the immune system. This review aimed to summarize the current knowledge of the cytokine profile in ITP and its potential implications for diagnosis, treatment, and prognosis. Several studies have reported that ITP patients have an altered cytokine profile from that of healthy individuals. Specifically, there is evidence of an imbalance of pro-inflammatory (interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ) and anti-inflammatory cytokines (IL-10, TGF-β). The cytokine profile in ITP appears to be heterogeneous, with different patterns observed in different subsets of patients. For example, some studies have reported a Th1-type cytokine profile, characterized by elevated levels of IFN-γ and TNF-α, while others have reported a Th2-type cytokine profile, characterized by elevated levels of IL-4 and IL-10. There is also evidence of a shift from a Th1 to a Th2 cytokine profile in some patients over time. The cytokine profile in ITP may have important implications for diagnosis, treatment, and prognosis. Targeting specific cytokines or cytokine pathways may also represent a promising therapeutic approach for ITP. Further studies are needed to better understand the heterogeneity of the cytokine profile in ITP and its potential implications for clinical management.
... It is assumed that the "IL7-IL7R" axis probably plays an important role in the processes of immunosenescence and that its assessment can be used as a diagnostic tool for this condition [35]. According to V. Nguyen et al., despite the fact that IL7 is a necessary factor for "lymphocyte homeostasis" and its effects on normal aging, a persistent increase in IL7 above the physiological level can disrupt this delicate balance [35]. ...
... It is assumed that the "IL7-IL7R" axis probably plays an important role in the processes of immunosenescence and that its assessment can be used as a diagnostic tool for this condition [35]. According to V. Nguyen et al., despite the fact that IL7 is a necessary factor for "lymphocyte homeostasis" and its effects on normal aging, a persistent increase in IL7 above the physiological level can disrupt this delicate balance [35]. This position is also supported by the fact that for the implementation of the homeostatic functions of IL7, intermittent signaling is required and not a persistent increase [36,37]. ...
Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study included 183 patients aged 40–64 years who underwent duplex scanning of the carotid and lower limb arteries at two visits with an interval of 12–24 months between examinations. Phenotyping of circulating lymphocytes and monocytes subpopulations were performed through flow cytometry. An increase in the number of circulating TLR4-positive intermediate monocytes (>447.0–467.0 cells/μL) was an independent predictor of the short-term progression of lower limb artery atherosclerosis (p < 0.0001) and polyvascular atherosclerosis (p = 0.003). The assessment of TLR4-positive monocytes significantly improved the prognostic model for the progression of lower limb arterial atherosclerosis (C-index 0.728 (0.642–0.815) versus 0.637 (0.539–0.735); p = 0.038). An increase in the number of circulating TLR4-positive intermediate monocytes was an independent predictor of the short-term progression of lower limb artery and polyvascular atherosclerosis. Their inclusion into models containing conventional risk factors significantly improved their prognostic effectiveness regarding lower limb artery atherosclerosis progression.
... 15,16 IL-7 has also been regularly described as a potential rescue therapy for immunosuppressed and/or immune senescent patients. 17 Ex vivo experiments demonstrated that IL-7 could expand naïve and memory T cells 18 and restored T cell functionalities of septic 19 and SARS-CoV-2-infected patients. 20 In addition, soluble IL-7 has been evaluated in many clinical trials in oncology, 21 HIV, 22 and more recently in sepsis 23 and COVID-19 infection. ...
Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell “rejuvenation.” These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients.
... Interleukin 7 (IL-7) is an example of an interleukin that is involved in the COVID-19 cytokine storm. IL-7 is a cytokine that has a function in immune system regulation [18,19]. Its participation in cytokine storms in COVID-19 is considered to be connected to its capacity to increase the generation and activation of immune cells such as T cells and B cells ( Figure 1). ...
Introduction: As the major mechanism for coronavirus disease 2019, cytokine storm-mediated organ
harm continues to dominate current understanding. Despite the first hyper-inflammatory phase, emerging data show that virus-induced poor host immunity may be the true cause of mortality in many individuals. Interleukin 7 (IL-7) is an interleukin that participates in the COVID-19 cytokine storm and regulates the immune system. Its role in COVID-19 cytokine storms is thought to be related to its ability to stimulate the formation and activation of immune cells such as T cells and B cells. This meta-analysis aims to determine the relationship, if any, between interleukin-7 and COVID-19 severity.
Methods: This study was planned as a systematic review and meta-analysis and followed the PRISMA guidelines. Four main electronic databases (Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) were searched from January 1st, 2020 to September 2nd, 2022, to find papers investigating the prognostic significance of interleukin-7 in COVID-19- hospitalized adults. Google Scholar was used in addition to the online database search. A random effects model was used to calculate mean differences and 95% confidence interval (CIs) as well as the I2 statistics for heterogeneity analysis.
Results: Seven papers were chosen for meta-analysis findings synthesis. All six trials reported interleukin-7 levels among severe and non-severe COVID-19 patients. Pooled analysis showed that IL-7 levels in the severe group were 62.79±81.03 pg/mL, compared to 33.39±56.54 pg/mL for the non- severe group (SMD = -0.17; 95%CI: -0.93 to 0.60; p=0.67).
Discussion: Available evidence suggests that elevated levels of IL-7 were not associated with the disease severity of COVID-19. While IL-7 levels alone may not have a substantial impact on COVID- 19 severity, the interaction between IL-7 and other cytokines, immune cells, and variables such as viral load and genetics should be investigated further.
