060 γc家族新成员:白细胞介素21

白细胞介素21(Interleukin 21,IL-21)是最近发现的γc家族新成员,和IL-2、IL-15、II-4高度同源,主要由活化的CD4+T细胞产生.IL-21受体复合体由特异的IL-21受体识别亚单位和γc信号传导亚单位组成,高表达于胸腺、骨髓基质细胞、外周B细胞和NK细胞.IL-21能促进骨髓NK细胞增殖与分化,与抗CD40抗体协同刺激B细胞增殖,与抗CD3抗体协同刺激T细胞增殖.     

γc家族新成员：白细胞介素2l

白细胞介素21(Interleukin 2l，IL-21)是最近发现的γc家族新成员，和IL-2、IL-15、IL-4高度同源，主要由活化的CD4^ T细胞产生。IL-21受体复合体由特异的IL-21受体识别亚单位和γc信号传导亚单位组成，高表达于胸腺、骨髓基质细胞、外周B细胞和NK细胞。IL-21能促进骨髓NK细胞增殖与分化，与抗CD40抗体协同刺激B细胞增殖，与抗CD3抗体协同刺激T细胞增殖。     

IL-21在自身免疫性疾病中的作用

白细胞介素21(IL-21)是IL-2家族中的新成员,主要由活化的CD4+T细胞产生.IL-21具有广泛的生物学功能,主要调节T细胞、B细胞、NK细胞的功能.近年来IL-21与自身免疫性疾病的关系得到了广泛的研究,为自身免疫性疾病的治疗提供了新的思路和方法.     

白细胞介素-38的生物学功能及其与银屑病的关系

白细胞介素(IL)-38是近年来发现的IL-1家族的一员,由T淋巴细胞、B淋巴细胞、NK细胞、上皮细胞分泌.IL-38的特异性受体IL-1Rrp2-Fc广泛表达于各种免疫细胞表面.IL-38作为IL-1受体拮抗剂可能通过与其受体IL-1 Rrp2-Fc结合来发挥生物学效应.IL-38在Th17细胞相关的自身免疫性疾病中发挥着重要的调节作用.研究发现,IL-38可通过抑制Th17细胞的产生来缓解银屑病的进程,因此,其靶向疗法将为自身免疫病的治疗带来希望.     

白细胞介素-21的免疫调节机制

白细胞介素-21（IL-21）是由激活的CD4^＋T细胞产生的细胞因子.IL-21受体（IL-21R）与IL-2R、IL-4R、IL-7R、ID9R、IL-15R等受体享有共同的受体γ链,广泛表达于免疫细胞上,介导各种免疫效应.IL-21能够增强免疫效应细胞增殖、抗原诱导的激活、克隆扩增,IFN-γ产生,以及NK细胞和T细胞的细胞毒效应.IL-21在被发现之初是作为抗肿瘤因子,最近发现IL-21与自身免疫和炎症性疾病具有相关性.     

IL-21的生物学功能及其在病毒感染中的作用

IL-21是最近发现的一种Ⅰ型细胞因子,由活化的CD4^＋T细胞产生,特别是Th2细胞。IL-21R存正常的淋巴组织包括脾、胸腺、淋巴结、外周血淋巴细胞、纤维化肺组织中都有表达。IL-21特异性结合IL-21R介导多种生物学效应,对不同阶段B、T淋巴细胞的分化和自然杀伤（NK）细胞的增殖均起重要作用。因此IL-21有着广泛的生物学功能,在各种疾病包括病毒感染中扮演着重要的角色。     

白细胞介素21研究进展

IL 2 1是一种新近发现的细胞因子 ,主要由CD4 + T细胞分泌的 ,与其受体结合后可以调节B细胞的增生 ,促进T细胞、NK细胞的增殖、分化并能提高NK细胞杀伤活性 ,IL 2 1与多种疾病的发生有关。本文就IL 2 1及其受体的产生、分子结构、生物学作用及与疾病关系的研究进展作一综述。     

白细胞介素21免疫学效应研究进展

白细胞介素21(Interleukin21,IL-21)是最近发现的一种细胞因子,主要由活化的CD4 T细胞产生,与IL-2、IL-15、IL-4等细胞因子具有高度同源性。IL-21具有广泛的生物学功能,能够调节体液和细胞介导的免疫应答,刺激T、B和NK细胞的增殖、活化和分化,并且对肿瘤细胞的生长有抑制作用。     

B7家族成员的研究新进展

B7分子属免疫球蛋白超家族成员,表达于多种免疫细胞和非免疫细胞上.抗原提呈细胞表面的B7分子与T细胞上的相应受体结合可提供T细胞活化的第二信号,从而调节和控制T细胞的活化、增殖及免疫应答.B7家族成员在感染、肿瘤以及自身免疫性疾病等发病机制中起着关键作用.选择性阻断协同刺激分子有望能成为临床治疗这些疾病的一种新途径.近...     

IL-21与疾病关系的研究进展

白细胞介素21(IL-21)是2000年被发现的细胞因子,作为IL-2细胞因子家族的新成员,参与多种免疫学功能,参与固有免疫应答和适应性免疫应答。IL-21具有多效性,与其受体结合后不仅可以促进淋巴样细胞的增殖,增强CD8+T细胞和自然杀伤细胞的细胞毒作用,还可诱导B细胞分化为浆细胞,促进CD4+T细胞向Th17分化。IL-21与多种疾病的发展也密切相关。本综述旨在介绍IL-21的生物学特性基础上,重点阐述它与疾病的关系的研究进展。     

Interleukin 21: a key player in lymphocyte maturation

The common gamma chain family of cytokine receptors plays a plethora of roles during the early development, activation, and terminal differentiation of the lymphocyte lineages. The most recently identified member of this family, the IL-21R, is expressed to varying degrees on B, T lymphocytes, and natural killer (NK) cells, whereas IL-21, is reportedly only produced by activated CD4+ T cells. In keeping with this expression pattern the IL-21:IL-21R interaction is important for the latter stages and function of all three lymphoid lineages. IL-21 is a regulator of A-cell differentiation to plasma cells as well as immunoglobulin class switching. In contrast, within the T-cell lineage, IL-21 acts as a co-stimulator of proliferation, enhances memory response, and modulates homeostasis. Within the innate immune system IL-21 has a role in the terminal differentiation of NK cells, enhancing cytotoxic function while also decreasing cellular viability. These immune maturation and stimulating functions have resulted in IL-21 being tested in a variety of models of immunity. In these contexts, IL-21 has shown very promising efficacy in a number of antitumor immune responses mediated by NK and or T lymphocytes.     

Expression, purification and identification of recombinant mouse interleukin 21 protein in E. coli

Interleukin 21 （IL-21） is a novel type I cytokine that is significantly homologous to IL-2, IL-4 and IL-15. Its receptor complex contains γc chain which is also a component of receptors for IL-2, IL-4, IL-7, IL-9 and IL-15, so there may be overlapping or relevancies in their biological functions. IL-21 is capable of co-stimulating mature T cells, B cells, NK cells, and of stimulating CD16 expression on the surface of NK cells to induce ADCC in innate immune response. It can also strengthen the anti-tumor effect of the cellular immunity, especially v/a enhancing the activities of NK and antigen specific CTL cells. Thus, IL-21 is a potential useful therapeutic molecule for immunotherapy of malignancies, by eliciting innate and adaptive anti-tumor immune responses in tumor-bearing hosts. In order to study the biological functions of IL-21, we constructed a mIL-21 prokaryotic expression plasmid and expressed the recombinant mIL-21 protein in E. coli in present study. The recombinant plasmid pET28a/mIL-21 with a carboxyl terminal His-tag was subcloned from the pcDNA3.1/mIL-21 and expressed in E. coli. The induced protein was detected by SDS-PAGE, and identified by Western-blot assay with anti-mIL-21 antibody. The recombinant protein was purified v/a Ni^＋ affinity chromatography, and renatured with GSH/GSSG system. Our mouse T cell proliferation experiment showed that the recombinant mIL-21 protein could enhance the mouse T cell proliferation either by itself alone or in the presence of Con A.     

IL-21与慢性乙型病毒性肝炎的关系研究

白细胞介素21是一类具有潜在的免疫调节作用、含有4个α螺旋结构的Ⅰ型细胞因子,主要由CD4+T和NKT细胞分泌产生。其受体分布极其广泛,通过与IL-21R结合后,IL-21参与子机体的多重免疫调节。如:促进Tfh、Th17等淋巴细胞增殖,增强CD8+T和NK细胞的细胞毒性,诱导B分化为浆细胞;同时又可抑制DC细胞的效应,促进B细胞和NK细胞调亡,以及负性调节Teg细胞的免疫抑制作用。免疫耐受是HBV病毒持续感染的根本原因,而IL-21在慢性乙肝病毒感染的清除及病毒抗原的血清学转换中可能发挥一定的调控作用。     

Analysis of gammac-dependent cytokines-mediated immunoregulation

In the study of interleukin-2 (IL-2) -induced signal transduction system, we identified and cloned the third component of IL-2 receptor, IL-2Rgamma chain. Functional high affinity IL-2 receptor consists of three subunits, alpha, beta and gamma chains. Interestingly not only IL-2 but also IL-4, IL-7, IL-9, IL-15 and IL-21 utilize the gamma chain as an essential component of each receptors. Therefore the gamma chain is now called as a common gamma chain (gammac). Moreover the gene of gammac is on the X chromosome, and mutations of gammac gene cause human X-linked severe combined immunodeficiency (X-SCID) characterized by a complete or profound defect of T cells and NK cells, and by the presence of dysfunctional B cells. The dysfunctions in IL-7- and IL-15-induced signal transduction cause the T cell and NK cell defect, respectively and dysfunctions in both IL-4- and IL-21-induced signal transduction cause the B cell dysfunction in X-SCID patients. Gene therapy is a good candidate for X-SCID treatment because only the HLA-matched bone marrow transplantation is an effective therapy. Unfortunately because of an unexpected adverse effect, such gene therapy using retrovirus vector is now aborted. IL-21 is a recently identified cytokine, which shares the gammac. IL-21 regulates the proliferation of T cells, the proliferation and differentiation of B cells, and the activation and expansion of NK cells. We demonstrated that human IL-21 was produced from activated CD4+ central and effector memory T cells but not from naive CD4+ T cells nor CD8+ T cells. Furthermore we found that IL-21 supported cytokine-driven proliferation of CD4+ helper T cells cooperatively with IL-7 and IL-15.     

Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes

Signaling lymphocytic activation molecule (SLAM) family receptors mediate important regulatory signals in immune cells, as a result of their exquisite ability to associate with members of the SLAM-associated protein (SAP) family of adaptors. As discussed herein, recent findings show that the SLAM and SAP families carry out pivotal functions in innate-like and conventional lymphocytes. They are critically needed for the development of innate-like lymphocytes such as NKT cells. In addition, they influence several of the functions of conventional lymphocytes, including the ability of CD4(+) T cells to secrete certain cytokines and mediate B cell help; CD8(+) T cell proliferation and cytokine production; NK cell-mediated cytotoxicity; and B cell antibody production. These unique functional properties appear to be facilitated by the ability of SLAM-related receptors to serve as self-ligands during homotypic interactions between immune cells. The importance of the SLAM-SAP pathway in normal immunity is highlighted by the finding that SAP is mutated in humans suffering from the immunodeficiency X-linked lymphoproliferative disease.     

IL-21 and IL-21 receptor

Interleukin (IL)-21 is a new member of the type I cytokine superfamily. Although it is most homologous to IL-15, it has a unique receptor chain, IL-21R, that pairs with the γ-common cytokine receptor chain. The first experiments examining the biology of the IL-21 pathway reveal that it is a cytokine with effects on natural killer (NK) cells, T cells, and B cells. Mice deficient in the IL-21 R have also been made, and are being examined for the effects of the IL-21/IL-21R pathway in vivo. Here we summarize our current knowledge of this new cytokine pathway, and its role in innate and adaptive immunity.     

Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis

Interleukin (IL)-21 is a CD4+ T-cell-derived cytokine, which is involved in innate and adaptive immune response. In this study, we analysed IL-21 receptor (IL-21R) expression in peripheral blood and synovial fluid mononuclear cells, and investigated the role of IL-21 in the induction of proinflammatory cytokine production by peripheral blood T cells (PB-T) and synovial fluid T cells (SF-T) from patients with rheumatoid arthritis (RA). Immunohistochemical staining demonstrated that IL-21R-positive cells were significantly increased in inflamed synovial tissues of RA patients compared with osteoarthritis (OA) and healthy controls. Flow cytometric analysis confirmed that IL-21R was mainly expressed in freshly isolated CD4, CD8, B and NK cells from peripheral blood and synovial fluid, but decreased gradually in T cells 24 h after anti-CD3 stimulation. PB- and SF-T cells from RA patients were more responsive to IL-21 when compared with controls. Importantly, isolated PB- or SF-T cells from RA patients, when stimulated with IL-21 and anti-CD3 MoAb, secreted markedly higher levels of TNF-alpha and IFN-gamma than controls. These data indicate that IL-21R is overexpressed in the inflamed synovial membrane and in peripheral blood or synovial fluid leukocytes of RA patients, and that IL-21 enhances local T-cell activation, proliferation and proinflammatory cytokine secretion. Thus, blockade of IL-21R signalling pathway may have a therapeutic potential in acute RA patients.     

IL-21: roles in immunopathology and cancer therapy

Cytokines are secreted signalling molecules with decisive effects on haematopoiesis, innate and adaptive immunity, and immunopathology. Interleukin (IL)-21 is a novel cytokine produced by activated CD4⁺ T cells and natural killer T (NKT) cells. IL-21 is part of a family of cytokines which include IL-2, -4, -7, -9 and -15 that all share the common IL-2 receptor γ chain (γ_c) in their individual receptor complexes. IL-21 receptor (IL-21R) is widely expressed on both myeloid and lymphoid cell lineages and IL-21 actions include co-stimulation of B cell differentiation and immunoglobulin (Ig) production, co-mitogen of T cells, and stimulation of NK and CD8⁺ T cell cytotoxic function. Initially, IL-21 was recognized for its anti-tumour effects in several preclinical tumour models, warranting its currently ongoing clinical development as a cancer immunotherapeutic. More recently, IL-21 has been associated with the development of a panel of autoimmune and inflammatory diseases, where neutralization of IL-21 has been suggested as a potential new therapy. In this review, we will cover the latest discoveries of IL-21 as a cancer therapy and its implications in immunopathologies.