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Cytokine Sep 2023Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a syndrome shaped by pathogen and host factors evolving over time....
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a syndrome shaped by pathogen and host factors evolving over time. During sepsis, the absolute number of lymphocytes decreases. CD4+ and CD8+ T cells, B cells, and NK cells are reduced. Lymphocytes are an essential element of the body's defence against pathogens. Interleukin 7 has strong anti-apoptotic properties and induces the proliferation of CD4+ and CD8+ T lymphocytes. IL-15 prompts the generation of mature NK cells in the bone marrow, plays an important role in the generation, cytotoxicity, and survival of CD8+ T lymphocytes, and is essential for the survival of natural killer T (NKT) and intestinal intraepithelial lymphocytes (IELs). The study highlights the importance of monitoring IL-7 levels in patients with sepsis and septic shock, as low levels of this cytokine were associated with an increased risk of mortality. Physicians should consider using IL-7 levels as a biomarker to identify patients who are at higher risk of mortality and may require more aggressive treatment.
Topics: Humans; Shock, Septic; Interleukin-7; Interleukin-15; Prognosis; Sepsis; Biomarkers
PubMed: 37348189
DOI: 10.1016/j.cyto.2023.156277 -
BMC Immunology Jul 2022Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8 T cell exhaustion. The mechanisms underlying...
BACKGROUND
Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8 T cell exhaustion. The mechanisms underlying CD8 T cell responses to IL-7 in melanoma remain not completely elucidated. We previously showed reduced IL-7 level in melanoma patients. Thus, the aim of this study was to investigate the effect of IL-7 regulation on CD127 expression and CD8 T cell responses in melanoma.
METHODS
Healthy controls and primary cutaneous melanoma patients were enrolled. Membrane-bound CD127 (mCD127) expression on CD8 T cells was determined by flow cytometry. Soluble CD127 (sCD127) protein level was measured by ELISA. Total CD127 and sCD127 mRNA level was measured by real-time PCR. CD8 T cells were stimulated with recombinant human IL-7, along with signaling pathway inhibitors. CD8 T cells were co-cultured with melanoma cell line, and the cytotoxicity of CD8 T cells was assessed by measurement of lactate dehydrogenase expression.
RESULTS
Plasma sCD127 was lower in melanoma patients compared with controls. The percentage of CD8 T cells expressing mCD127 was higher, while sCD127 mRNA level was lower in peripheral and tumor-infiltrating CD8 T cells from melanoma patients. There was no significant difference of total CD127 mRNA expression in CD8 T cells between groups. IL-7 stimulation enhanced total CD127 and sCD127 mRNA expression and sCD127 release by CD8 T cells. However, mCD127 mRNA expression on CD8 T cells was not affected. This process was mainly mediated by phosphatidylinositol 3-kinase (PI3K) pathway. CD8 T cells from melanoma patients exhibited decreased cytotoxicity. IL-7 stimulation promoted CD8 T cell cytotoxicity, while inhibition of PI3K dampened IL-7-induced elevation of CD8 T cell cytotoxicity.
CONCLUSION
The current data suggested that insufficient IL-7 secretion might contribute to CD8 T cell exhaustion and CD127 dysregulation in patients with primary cutaneous melanoma.
Topics: CD8-Positive T-Lymphocytes; Humans; Interleukin-7; Interleukin-7 Receptor alpha Subunit; Melanoma; Phosphatidylinositol 3-Kinases; RNA, Messenger; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35850640
DOI: 10.1186/s12865-022-00509-0 -
Nature Communications Jun 2022Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of...
Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity.
Topics: Animals; Cell Proliferation; Humans; Interleukin-7; Mice; Neoplasms; Receptors, Chimeric Antigen; Recombinant Fusion Proteins; T-Lymphocytes
PubMed: 35697686
DOI: 10.1038/s41467-022-30860-0 -
Frontiers in Immunology 2019Innate lymphoid cells (ILCs) are a group of immune cells that are important for defense against pathogens, tissue repair, and lymphoid organogenesis. They share similar... (Review)
Review
Innate lymphoid cells (ILCs) are a group of immune cells that are important for defense against pathogens, tissue repair, and lymphoid organogenesis. They share similar characteristics with various subsets of helper T cells but lack specific antigen receptors. Interleukin-7 (IL-7) and thymic stromal lymphopoietin (TSLP) are cytokines that engage the IL-7Rα and have major roles in dictating the fate of ILCs. Recent advances in the field have revealed transcriptional programs associated with ILC development and function. In this article, we will review recent studies of the role of IL-7 and TSLP in ILC development and function during infection and inflammation.
Topics: Animals; Cytokines; Humans; Immunity, Innate; Infections; Inflammation; Interleukin-7; Lymphocytes; Receptors, Interleukin-7
PubMed: 31921158
DOI: 10.3389/fimmu.2019.02897 -
Immunological Reviews May 2019Studies over the last decade uncovered overlapping niches for hematopoietic stem cells (HSCs), multipotent progenitor cells, common lymphoid progenitors, and early B... (Review)
Review
Studies over the last decade uncovered overlapping niches for hematopoietic stem cells (HSCs), multipotent progenitor cells, common lymphoid progenitors, and early B cell progenitors. HSC and lymphoid niches are predominantly composed by mesenchymal progenitor cells (MPCs) and by a small subset of endothelial cells. Niche cells create specialized microenvironments through the concomitant production of short-range acting cell-fate determining cytokines such as interleukin (IL)-7 and stem cell factor and the potent chemoattractant C-X-C motif chemokine ligand 12. This type of cellular organization allows for the cross-talk between hematopoietic stem and progenitor cells with niche cells, such that niche cell activity can be regulated by the quality and quantity of hematopoietic progenitors being produced. For example, preleukemic B cell progenitors and preB acute lymphoblastic leukemias interact directly with MPCs, and downregulate IL-7 expression and the production of non-leukemic lymphoid cells. In this review, we discuss a novel model of B cell development that is centered on cellular circuits formed between B cell progenitors and lymphopoietic niches.
Topics: Animals; B-Lymphocytes; Cell Differentiation; Cellular Microenvironment; Chemokine CXCL12; Endothelial Cells; Hematopoietic Stem Cells; Humans; Interleukin-7; Lymphopoiesis; Mesenchymal Stem Cells; Stem Cell Niche
PubMed: 30977190
DOI: 10.1111/imr.12749 -
Nature Aging Mar 2022Impaired T cell immunity with aging increases mortality from infectious disease. The branching of Asparagine-linked glycans is a critical negative regulator of T cell...
Impaired T cell immunity with aging increases mortality from infectious disease. The branching of Asparagine-linked glycans is a critical negative regulator of T cell immunity. Here we show that branching increases with age in females more than males, in naïve more than memory T cells, and in CD4 more than CD8 T cells. Female sex hormones and thymic output of naïve T cells (T) decrease with age, however neither thymectomy nor ovariectomy altered branching. Interleukin-7 (IL-7) signaling was increased in old female more than male mouse T cells, and triggered increased branching. N-acetylglucosamine, a rate-limiting metabolite for branching, increased with age in humans and synergized with IL-7 to raise branching. Reversing elevated branching rejuvenated T cell function and reduced severity of infection in old female mice. These data suggest sex-dimorphic antagonistic pleiotropy, where IL-7 initially benefits immunity through T maintenance but inhibits T function by raising branching synergistically with age-dependent increases in N-acetylglucosamine.
Topics: Humans; Male; Female; Animals; Mice; CD8-Positive T-Lymphocytes; Acetylglucosamine; Interleukin-7; Aging; Polysaccharides
PubMed: 35528547
DOI: 10.1038/s43587-022-00187-y -
Arthritis and Rheumatism Aug 2013
Topics: Animals; Autoimmune Diseases; Interleukin-7; Sjogren's Syndrome; Submandibular Gland; Th1 Cells
PubMed: 23666552
DOI: 10.1002/art.38002 -
Oncoimmunology 2022Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment...
Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment can lead to a number of adverse events. Interleukin 7 has shown promising results in clinical trials, but anti-cancer effect was limited, in part due to a low concentration of the cytokine within the tumor. We hypothesized that arming an oncolytic adenovirus with Interleukin 7, enabling high expression localized to the tumor microenvironment, would overcome systemic delivery issues and improve therapeutic efficacy. We evaluated the effects of Ad5/3-E2F-d24-hIL7 (TILT-517) on tumor growth, immune cell activation and cytokine profiles in the tumor microenvironment using three clinically relevant animal models and tumor cultures. Our data showed that local treatment of tumor bearing animals with Ad5/3- E2F-d24-hIL7 significantly decreased cancer growth and increased frequency of tumor-infiltrating cells. Ad5/3-E2F-d24-hIL7 promoted notable upregulation of pro-inflammatory cytokines, and concomitant activation and migration of CD4+ and CD8 + T cells. Interleukin 7 expression within the tumor was positively correlated with increased number of cytotoxic CD4+ cells and IFNg-producing CD4+ and CD8+ cells. These findings offer an approach to overcome the current limitations of conventional IL7 therapy and could therefore be translated to the clinic.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Cell Line, Tumor; Cytokines; Interleukin-7; Lymphocytes, Tumor-Infiltrating; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 35845722
DOI: 10.1080/2162402X.2022.2096572 -
Current Diabetes Reports May 2016Immunomodulation of the autoreactive T cell response is considered a major strategy to control beta-cell autoimmunity, both in the natural history of type 1 diabetes and... (Review)
Review
Immunomodulation of the autoreactive T cell response is considered a major strategy to control beta-cell autoimmunity, both in the natural history of type 1 diabetes and in islet transplantation, which can be affected by autoimmunity recurrence. So far, these strategies have had modest results, prompting efforts to define novel cellular and molecular targets to control autoreactive T cell expansion and activation. Novel findings highlighted the important role of the homeostatic cytokine interleukin-7 in inducing proliferation and differentiation of autoreactive T cell clones that causes beta-cell autoimmunity. In this review, we discuss recent evidences and novel findings on the role of IL-7 mediated homeostatic T cell proliferation in the process of beta-cell destruction and evidences of how targeting IL-7 and its receptor could be an innovative and effective strategy to control beta-cell autoimmunity.
Topics: Animals; Autoimmunity; Cell Proliferation; Homeostasis; Humans; Insulin-Secreting Cells; Interleukin-7; T-Lymphocytes
PubMed: 26983628
DOI: 10.1007/s11892-016-0731-9 -
International Journal of Cell Cloning Jan 1990Interleukin 7 (IL-7) is a cytokine initially referred to as pre-B cell growth factor because of its growth-promoting activity for cells early in the B lymphocyte... (Review)
Review
Interleukin 7 (IL-7) is a cytokine initially referred to as pre-B cell growth factor because of its growth-promoting activity for cells early in the B lymphocyte lineage. Subsequent to IL-7 gene cloning and expression, IL-7 was also found to influence the activity of cells in the T lineage. Some of the effects of IL-7 on B and T lymphocyte behavior, both in vitro and in vivo, are discussed here. The growth of pre-B cells in Whitlock-Witte long-term bone marrow cultures [1] provided the basis for the cloning of IL-7 [2]. Such cultures consist of at least two cellular elements: 1) a stromal cell layer and 2) lymphoid cells growing in clusters around the stromal cells. A cDNA encoding IL-7 was cloned utilizing a direct expression cloning strategy. A transformed stromal cell line was used as a source of RNA from which a cDNA library was constructed, inserted into a mammalian expression vector and expressed in COS 7 cells. The COS cells were then screened for secretion of IL-7 into the culture medium as defined by the ability to support stromal cell-independent growth of the lymphoid elements from long-term Whitlock-Witte cultures. In addition to its effects on cells from long-term marrow cultures, IL-7 stimulates growth of cells in cultures of fresh bone marrow [3]. Cells from whole bone marrow plated in semisolid agar form colonies in the presence of IL-7. If the marrow is first enriched for cells expressing the B220 antigen before culture in IL-7, the plating efficiency is increased dramatically.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; B-Lymphocytes; Cyclophosphamide; In Vitro Techniques; Interleukin-7; Lymphocyte Activation; T-Lymphocytes
PubMed: 2182735
DOI: 10.1002/stem.5530080715