BACKGROUND: Interleukin-7 receptor (IL-7R) alpha-deficient mice have small numbers of B cells and alpha beta T cells in periphery, they totally lack gamma sigma T cells. In addition, the V-J recombination and transcription of TCRgamma genes is also severely impaired in IL-7Ralpha-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCRgamma locus, and promotes V-J recombination and gamma sigma T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic gamma sigma T cell development are largely unknown. METHODS: To clarify the role of the IL-7 receptor in proliferation and survival of gamma sigma T cells, we introduced the TCR gamma sigma transgene, Vgamma2/ Vsigma5, into IL-7Ralpha-deficient mice, and investigated the development of gamma sigma T cells. RESULTS: We found that Vgamma2/Vsigma5 transgene restored gamma sigma T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of gamma sigma T cells in the thymus and the spleen of these mice. CONCLUSION: Taken together, this study revealed that the IL-7Ralpha is indispensable for proliferation and survival mainly in thymic gamma sigma T cell development.
Animals ; B-Lymphocytes ; Epithelium ; Interleukin-7* ; Intestine, Small ; Mice ; Receptors, Interleukin-7 ; Recombination, Genetic ; Spleen ; T-Lymphocytes ; Thymus Gland ; Transgenes

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.
Cytokines ; Homeostasis ; Interferons ; Interleukin-1 ; Interleukin-10 ; Interleukin-11 ; Interleukin-12 ; Interleukin-15 ; Interleukin-17 ; Interleukin-23 ; Interleukin-27 ; Interleukin-3 ; Interleukin-33 ; Interleukin-4 ; Interleukin-6 ; Interleukin-7 ; Interleukin-8 ; Macrophage Colony-Stimulating Factor ; Necrosis ; Osteoblasts ; Osteoclasts ; RANK Ligand

OBJECTIVE: To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival. METHODS: Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated. RESULTS: Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05). CONCLUSION IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Cytokines/metabolism* ; Epstein-Barr Virus Infections/complications* ; Interleukin-6 ; Clinical Relevance ; Interleukin-7 ; Interleukin-8 ; Interleukin-9 ; Chemokines ; Interferons

We investigated the effects of beta-glucan purified from Paenibacillus polymyxa JB115 on the viability and proliferation of splenocytes. Splenocytes play a critical role in host immunity. MTT assays and trypan blue exclusion tests revealed that beta-glucan significantly promoted the viability and proliferation of splenocytes over a range of concentrations. However, there was no specific subset change. beta-glucan protected splenocytes from cytokine withdrawal-induced spontaneous cell death. For further mechanistic studies, ELISA assay revealed that beta-glucan enhanced the expression of anti-apoptotic molecules and interleukin 7 (IL-7), a cytokine critical for lymphocyte survival. We also investigated the IL-2 dependency of beta-glucan-treated splenocytes to determine if treated cells could still undergo clonal expansion. In flow cytometric analysis, beta-glucan induced increased levels of the activation marker CD25 on the surface of splenocytes and beta-glucan-treated splenocytes showed higher proliferation rates in response to IL-2 treatment. This study demonstrates that beta-glucan can enhance the survival of splenocytes and provides valuable information to broaden the use of beta-glucan in research fields.
Animals ; Cell Death ; Dependency (Psychology) ; Diminazene ; Enzyme-Linked Immunosorbent Assay ; Interleukin-2 ; Interleukin-7 ; Lymphocytes ; Mice ; Paenibacillus ; Plasmodiophorida ; Trypan Blue

BACKGROUND: A crucial limitation of DNA vaccines is its weak immunogenicity, especially in terms of eliciting antibody responses in non-human primates or humans; therefore, it is essential to enhance immune responses to vaccination for the development of successful DNA vaccines for humans. METHODS: Here, we approached this issue by evaluating interleukin-7 (IL-7) as a genetic adjuvant in cynomolgus monkeys immunized with multigenic HCV DNA vaccine. RESULTS: Codelivery of human IL-7 (hIL-7)-encoding DNA appeared to increase DNA vaccine-induced antibody responses specific for HCV E2 protein, which plays a critical role in protecting from HCV infection. HCV-specific T cell responses were also significantly enhanced by codelivery of hIL-7 DNA. Interestingly, the augmentation of T cell responses by codelivery of hIL-7 DNA was shown to be due to the enhancement of both the breadth and magnitude of immune responses against dominant and subdominant epitopes. CONCLUSION: Taken together, these findings suggest that the hIL-7-expressing plasmid serves as a promising vaccine adjuvant capable of eliciting enhanced vaccine-induced antibody and broad T cell responses.
Antibody Formation ; DNA ; Humans ; Interleukin-7 ; Macaca fascicularis ; Plasmids ; Primates ; Vaccination ; Vaccines, DNA

OBJECTIVE: The patients of endometriosis may complain of dysmenorrhea, pelvic pain, and dyspareunia, but may be asymptomatic. We studied on the correlation between the pain and the psychologic stress, Also, we studied on the correlation between serum CA-l25 levels and the psychologic stress. METHODS: The data was obtained from il7 endometriosis patients. Psychological stress was studied with STAI(Stait-Trait Anxiety Inventory) and BDI(Beck Depression Inventory). We compared the degree of anxiety and depression according to existence of pain and the duration of pain. Also we examed the scores of STAI and BDI according to the level of serum CA-125. RESULTS: The pain group had more depression and anxiety, in comparison to the pain-free group. And the depression and anxiety significantly increased in long-term pain group. There was no correlation between the level of serum CA-125 and the depression,or axiety. CONCLUSION: The pain of endometriosis may play a role of pychological stress to the patients, so it seems to increase depression and anxiety.
Anxiety ; Depression ; Dysmenorrhea ; Dyspareunia ; Endometriosis* ; Female ; Humans ; Interleukin-7 ; Pelvic Pain ; Stress, Psychological*

OBJECTIVEMutation in the interleukin-7 receptor-alpha (IL-7R alpha) chain causes a rare type of severe combined immunodeficiency (SCID) with presence of NK cells in the peripheral blood. Here we report the molecular and clinical characterization of a compound heterozygosity mutation in the interleukin-7 receptor-alpha gene that resulted in SCID in a patient firstly from China.

METHODA 5 month-old male patient and his parents were enrolled in this study. Since 15 days of age, the patient had had recurrent fever, persistent cough and diarrhea. He was in poor general condition with pyorrhea and ulceration of the BCG scar. His brother died of severe infection at 4 months of age. He was initially diagnosed as SCID according to clinical manifestation and immunological analysis. A panel of SCID candidate genes including IL-2RG, RAG1/RAG2 and IL-7R alpha of patient and his parents were amplified by polymerase chain reaction (PCR) from genomic DNA. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the IL-7R alpha transcripts. Sequencing was performed directly on the PCR products forward and reversely.

RESULTThe serum immunoglobulin (Ig) profile was IgG 6867 mg/L (normal range, 3050 - 8870 mg/L); IgM 206 mg/L and IgA 249 mg/L, IgE 2.3 IU/ml (normal range < 150 IU/ml). The patient was treated with IVIG previously. There were no T-cells but increased percentage of B-cells (58%) and NK cells (42%) in the peripheral blood was found. Needle biopsies from enlarged axillary lymph node was identified positive for Mycobacterium bovis under microscope and by culture. The patient had a compound heterozygosity mutation in the IL-7R alpha gene:on one allele, there was a splice-junction mutation in intron 4 (intron 4(+1)G > A), for which his father was a carrier; whereas on the other allele, a nonsense mutation at position 638 in exon 5 with a premature stop codon (638 C > T, R206X) was identified, for which his mother was a carrier. The splice-junction mutation in intron 4 of IL-7R alpha was firstly reported. The IL-7R alpha mRNA expression of the patient was remarkably reduced whereas the parents had relatively normal IL-7R alpha mRNA expression. IL-7R alpha cDNA of the patient was amplified by nested PCR. The PCR products were purified, cloned with a TA Cloning Kit and sequenced directly. A 64 bp deletion was found in exon 4 of IL-7R alpha. No mutation was found in IL-2RG and RAG1/RAG2 of the patient and his parents.

CONCLUSIONThis is the first case with a compound heterozygosity mutation in the IL-7R receptor alpha gene and T-B+NK+ phenotype from China. Intron 4(+1)G > A was a novel mutation.

DNA ; Genome, Human ; Heterozygote ; Humans ; Infant ; Male ; Mutation ; Receptors, Interleukin-7 ; genetics ; Severe Combined Immunodeficiency ; genetics

OBJECTIVEInterleukin 7 (IL-7) and its receptor（IL-7R）are essential for normal T-cell development and homeostasis. This study was aimed to investigate the IL-7R mutation and its clinical significance in adult patients with adult acute lymphoblastic leukemia (ALL), particularly in T-ALL.

METHODSThe exons of IL-7R were amplified, cloned and sequenced in 144 adult patients with ALL; the frequency, position and lypes of IL-7R mutation were detected and their correlation with clinical features was analyzed.

RESULTS7.3% of T-ALL and 1.1% of B-ALL showed somatic IL-7R mutations which located at exon 6 and exon 5, respectively. Moreover, the IL-7R mutation was associated with poor clinical outcome in adult ALL patients. Furthermore, the co-existence of IL-7R mutation with NOTCH1 mutations and/or PHF6 mutation in T-ALL was observed.

CONCLUSIONIL-7R mulation and its associated signaling pathways may play an important role in the pathogenesis of T-ALL.

Adult ; Exons ; Humans ; Mutation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Receptors, Interleukin-7

OBJECTIVETo detect the effects of human interleukin-1beta (IL-1beta) and Dexamethasone (DEX) on the expression level of keratinocyte growth factor (KGF) in cultured human fibroblasts of normal oral and oral lichen planus (OLP) mucosa.

METHODSThree concentration gradients of IL-1beta and DEX were added to cultured fibroblasts of human normal oral and OLP mucosa respectively. 72 hours later, the supernatant was harvested for the detection of KGF concentration with enzyme linked immunosorbent assay (ELISA). Total RNA of the fibroblasts was extracted and reverse transcribed. The resulting cDNA was then amplified by polymerase chain reaction (PCR) to detect the KGF mRNA.

RESULTSThe results of the ELISA and PCR showed that the expression levels of KGF protein and mRNA were higher if the cells were treated with IL-1beta. However, the expression levels of KGF protein and mRNA were significantly reduced if the fibroblasts were treated with DEX.

CONCLUSIONIL-1beta can promote KGF expression levels of cultured normal oral and OLP fibroblasts, and it is concentration-dependent. While DEX can inhibit KGF expression of cultured normal oral and OLP fibroblasts, and it is also concentration-dependent.

Cells, Cultured ; Dexamethasone ; Fibroblast Growth Factor 7 ; Fibroblasts ; Humans ; Interleukin-1beta ; RNA, Messenger

The aim of this study was to compare cell proliferation and function of the T cells acquired under various culture conditions for establishing a simple, safe and efficient cell expansion protocol in vitro. The peripheral blood mononuclear cells (PBMNC) were isolated and stimulated with autologous dendritic cells (DC) and EBV-transformed B lymphoblastoid cell line (BLCL) weekly. The cell proliferation test, flow cytometry with PI and Annexin V double staining, Cr release test and ELISPOT test were used to detect the cell expansion level, frequency of IFN-γ producing T cells, killing activity of antigen-specific T cells, cell apoptotic status and cell differentiation potential, respectively. The results indicated that use of IL-2 combined with IL-7 and IL-15 resulted in the highest cell expansion comparing to the use of IL-2 alone and the use of CD3/28 Microbeads. Also the cells obtained under cultivating with IL-2, IL-7 and IL-15 together showed high frequency of IFN-γ producing cells, strong killing activity, high viability and high differentiation potential with large portion of CD3(+)CD8(+) population among the T cells. It is concluded that a protocol is established in which the use of IL-2 combined with IL-7 and IL-15 induces the biggest cell expansion, expanded cells show high viability, strong differentiation potential, high frequency of IFN-γ producing cells and strong killing activity.
Cell Line, Transformed ; Cell Proliferation ; Cell Separation ; Dendritic Cells ; cytology ; metabolism ; Humans ; Interleukin-15 ; pharmacology ; Interleukin-2 ; pharmacology ; Interleukin-7 ; pharmacology ; T-Lymphocytes ; cytology ; drug effects ; metabolism