Genomes and Genes
Gene Symbol: Il15
Description: interleukin 15
Alias: AI503618, IL-15, interleukin-15
- Mattei F, Schiavoni G, Belardelli F, Tough D. IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J Immunol. 2001;167:1179-87 pubmed..These results identify IL-15 as a stimulatory cytokine for DCs with the potential for autocrine activity and link its effects to expression of IFN-alphabeta. ..
- Nakazato K, Yamada H, Yajima T, Kagimoto Y, Kuwano H, Yoshikai Y. Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice. J Immunol. 2007;178:757-64 pubmed
- Bianchi T, Gasser S, Trumpp A, MacDonald H. c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell homeostasis. Blood. 2006;107:3992-9 pubmed..Collectively, our data identify c-Myc as a novel downstream component of the IL-15-dependent pathway controlling homeostatic proliferation of memory CD44(high) CD8 T cells. ..
- Sandau M, Schluns K, Lefrancois L, Jameson S. Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells. J Immunol. 2004;173:6537-41 pubmed..These data argue that soluble forms of IL-15 are irrelevant for physiological responses to this cytokine, and the implications of this finding are discussed. ..
- Ferrari Lacraz S, Zanelli E, Neuberg M, Donskoy E, Kim Y, Zheng X, et al. Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents disease development and progression in murine collagen-induced arthritis. J Immunol. 2004;173:5818-26 pubmed..Our study suggests that the effective targeting of IL-15R-triggered events with CRB-15 can be of therapeutic importance in the treatment of rheumatoid arthritis. ..
- Mortier E, Advincula R, Kim L, Chmura S, Barrera J, Reizis B, et al. Macrophage- and dendritic-cell-derived interleukin-15 receptor alpha supports homeostasis of distinct CD8+ T cell subsets. Immunity. 2009;31:811-22 pubmed publisher..Moreover, they demonstrate the diversity, specification, and geographic restriction of cytokine signals. ..
- Yajima T, Yoshihara K, Nakazato K, Kumabe S, Koyasu S, Sad S, et al. IL-15 regulates CD8+ T cell contraction during primary infection. J Immunol. 2006;176:507-15 pubmed..These results suggest that IL-15 plays a critical role in protecting effector CD8+ T cells from apoptosis during the contraction phase following a microbial infection via inducing antiapoptotic molecules. ..
- Gomez Nicola D, Spagnolo A, Guaza C, Nieto Sampedro M. Aggravated experimental autoimmune encephalomyelitis in IL-15 knockout mice. Exp Neurol. 2010;222:235-42 pubmed publisher..How these findings are contributing to the aggravated EAE development in IL-15 KO mice remain unclear and need to be further investigated. ..
- Ohteki T, Tada H, Ishida K, Sato T, Maki C, Yamada T, et al. Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. J Exp Med. 2006;203:2329-38 pubmed..Collectively, these data indicate the importance of DC-derived IL-15 as a mediator of inflammatory responses in vivo. ..
- Colpitts S, Stonier S, Stoklasek T, Root S, Aguila H, Schluns K, et al. Transcriptional regulation of IL-15 expression during hematopoiesis. J Immunol. 2013;191:3017-24 pubmed publisher..Thus, IL-15 expression is coordinated with cellular fate in myeloid versus lymphoid immune cells. ..
- van der Windt G, Everts B, Chang C, Curtis J, Freitas T, Amiel E, et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2012;36:68-78 pubmed publisher..These results show how cytokines control the bioenergetic stability of memory T cells after infection by regulating mitochondrial metabolism. ..
- Vonarbourg C, Mortha A, Bui V, Hernandez P, Kiss E, Hoyler T, et al. Regulated expression of nuclear receptor ROR?t confers distinct functional fates to NK cell receptor-expressing ROR?t(+) innate lymphocytes. Immunity. 2010;33:736-51 pubmed publisher..Our data also define a previously unappreciated role of ROR?t? NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases...
- Satoh Takayama N, Vosshenrich C, Lesjean Pottier S, Sawa S, Lochner M, Rattis F, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29:958-70 pubmed publisher..RORgammat-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces...
- Zhang M, Yao Z, Dubois S, Ju W, Müller J, Waldmann T. Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer. Proc Natl Acad Sci U S A. 2009;106:7513-8 pubmed publisher..The findings from this study provide the scientific basis for clinical trials using the combination regimen of IL-15 with an anti-CD40 antibody for the treatment of patients with cancer. ..
- Vosshenrich C, Ranson T, Samson S, Corcuff E, Colucci F, Rosmaraki E, et al. Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J Immunol. 2005;174:1213-21 pubmed..Surprisingly, the few residual NK cells generated in absence of IL-15 appear relatively mature, expressing a variety of Ly49 receptors and demonstrating lytic and cytokine production capacity. ..
- Watkins S, Li B, Richardson K, Head K, Egilmez N, Zeng Q, et al. Rapid release of cytoplasmic IL-15 from tumor-associated macrophages is an initial and critical event in IL-12-initiated tumor regression. Eur J Immunol. 2009;39:2126-35 pubmed publisher..In this context, the functional plasticity and pro-immunogenic potential of TAM may constitute a significant and unappreciated target in existing cytokine therapies. ..
- Ohteki T, Suzue K, Maki C, Ota T, Koyasu S. Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response. Nat Immunol. 2001;2:1138-43 pubmed..This shows that the IL-15-IL-15R interaction is critical in early activation of antigen-presenting cells and plays an important role in the innate immune system. ..
- Gordy L, Bezbradica J, Flyak A, Spencer C, Dunkle A, Sun J, et al. IL-15 regulates homeostasis and terminal maturation of NKT cells. J Immunol. 2011;187:6335-45 pubmed publisher..Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-x(L), and effector differentiation, which is consistent with a role of T-bet in regulating terminal maturation. ..
- Bergamaschi C, Bear J, Rosati M, Beach R, Alicea C, Sowder R, et al. Circulating IL-15 exists as heterodimeric complex with soluble IL-15R? in human and mouse serum. Blood. 2012;120:e1-8 pubmed publisher..Analysis of the form of IL-15 present in either normal or lymphodepleted mice agrees with the human data. These results have important implications for development of assays and materials for clinical applications of IL-15. ..
- Schulthess J, Meresse B, Ramiro Puig E, Montcuquet N, Darche S, Begue B, et al. Interleukin-15-dependent NKp46+ innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes. Immunity. 2012;37:108-21 pubmed publisher..Preliminary evidence suggests that this pathway might operate in Crohn's disease. ..
- Quinn L, Anderson B, Conner J, Wolden Hanson T. IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle PPAR?, SIRT1, PGC-1?, and PGC-1? expression in male mice. Endocrinology. 2013;154:232-45 pubmed publisher..These findings support a role for IL-15 in induction of exercise endurance, oxidative metabolism, and skeletal muscle molecular adaptations induced by physical training. ..
- Steel J, Ramlogan C, Yu P, Sakai Y, Forni G, Waldmann T, et al. Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help. Cancer Res. 2010;70:1072-81 pubmed publisher..Coexpression of IL-15 and IL-15Ralpha in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4(+) T-helper function. ..
- Sanos S, Bui V, Mortha A, Oberle K, Heners C, Johner C, et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol. 2009;10:83-91 pubmed publisher..IL-22 released by these cells promoted the production of antimicrobial molecules important in the maintenance of mucosal homeostasis. ..
- Kuwajima S, Sato T, Ishida K, Tada H, Tezuka H, Ohteki T. Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation. Nat Immunol. 2006;7:740-6 pubmedThe function of interleukin 15 (IL-15) in unmethylated CpG oligodeoxynucleotide (CpG)-induced immune responses remains unknown...
- Anderson D, Johnson L, Glaccum M, Copeland N, Gilbert D, Jenkins N, et al. Chromosomal assignment and genomic structure of Il15. Genomics. 1995;25:701-6 pubmed..Murine IL-15 cDNA and genomic clones were isolated and characterized. The murine Il15 gene was found to consist of eight exons spanning at least 34 kb and was localized to the central region of mouse ..
- Nguyen K, Salazar Mather T, Dalod M, Van Deusen J, Wei X, Liew F, et al. Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. J Immunol. 2002;169:4279-87 pubmed
- Ohta N, Hiroi T, Kweon M, Kinoshita N, Jang M, Mashimo T, et al. IL-15-dependent activation-induced cell death-resistant Th1 type CD8 alpha beta+NK1.1+ T cells for the development of small intestinal inflammation. J Immunol. 2002;169:460-8 pubmed..The model may contribute to understanding the role of CD8(+) T cells in human Crohn's disease involving the SI. ..
- Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity. 2007;26:503-17 pubmed..Our data define a unique in vivo role of DCs for the priming of NK cells, revealing a striking and previously unappreciated homology to T lymphocytes of the adaptive immune system. ..
- Ranson T, Vosshenrich C, Corcuff E, Richard O, Muller W, Di Santo J. IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood. 2003;101:4887-93 pubmed..Finally, although NK cells bear functional inhibitory Ly49 receptors for MHC class I molecules, the presence or absence of specific ligands on host cells did not influence the survival or homeostatic expansion of donor NK cells. ..
- Rückert R, Brandt K, Bulanova E, Mirghomizadeh F, Paus R, Bulfone Paus S. Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses. Eur J Immunol. 2003;33:3493-503 pubmed..Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeutic modulation of clinically relevant DTH reactions. ..
- Munger W, DeJoy S, Jeyaseelan R, Torley L, Grabstein K, Eisenmann J, et al. Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. Cell Immunol. 1995;165:289-93 pubmed..These results support the view that interleukin-15 exhibits a therapeutic index that is superior to interleukin-2. ..
- Umemura M, Nishimura H, Hirose K, Matsuguchi T, Yoshikai Y. Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis bacillus Calmette-Guérin infection via augmentation of NK and T cytotoxic 1 responses. J Immunol. 2001;167:946-56 pubmed..Thus, overexpression of IL-15 in vivo enhanced protection against BCG infection via augmentation of NK and T cytotoxic 1 responses. ..
- Marks Konczalik J, Dubois S, Losi J, Sabzevari H, Yamada N, Feigenbaum L, et al. IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci U S A. 2000;97:11445-50 pubmed..IL-15 thus seems to contribute to enhanced immune memory by selectively propagating memory T cells and by blocking T cell death mediated by IL-2. ..
- Sun J, Ma A, Lanier L. Cutting edge: IL-15-independent NK cell response to mouse cytomegalovirus infection. J Immunol. 2009;183:2911-4 pubmed publisher..Together, these findings demonstrate a previously unrecognized independence of NK cells on IL-15 or other common gamma signaling cytokines during their response against viral infection. ..
- Schluns K, Williams K, Ma A, Zheng X, Lefrancois L. Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells. J Immunol. 2002;168:4827-31 pubmed..IL-15Ralpha expression was low on naive CD8 T cells, up-regulated on Ag-specific effector cells, and sustained on memory cells. Thus, IL-15 was important for the generation and the subsequent maintenance of antiviral memory CD8 T cells. ..
- Dubois S, Waldmann T, Müller J. Survival adjustment of mature dendritic cells by IL-15. Proc Natl Acad Sci U S A. 2005;102:8662-7 pubmed..These findings support the hypothesis that DCs mediate the effect of IL-15 on CD8+/CD44(hi) memory phenotype T cells. ..
- Lenz D, Kurz S, Lemmens E, Schoenberger S, Sprent J, Oldstone M, et al. IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory. Proc Natl Acad Sci U S A. 2004;101:9357-62 pubmed..We propose that homeostatic control of antiviral CD4(+) and CD8(+) T cell memory is fundamentally similar and characterized by quantitative, rather than qualitative, differences. ..
- Combe C, Moretto M, Schwartzman J, Gigley J, Bzik D, Khan I. Lack of IL-15 results in the suboptimal priming of CD4+ T cell response against an intracellular parasite. Proc Natl Acad Sci U S A. 2006;103:6635-40 pubmed..Furthermore, based on these observations, targeting of IL-15 should have a beneficial effect on individuals suffering from CD4+ T cell-mediated autoimmune diseases. ..
- Musikacharoen T, Oguma A, Yoshikai Y, Chiba N, Masuda A, Matsuguchi T. Interleukin-15 induces IL-12 receptor beta1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. Blood. 2005;105:711-20 pubmed..Thus, IL-15 induces chromatin remodeling of the IL12RB1 gene promoter, increasing IL12RB1 mRNA expression in synergy with IFN-gamma through the recruitment of PU.1 and IRF3. ..
- Nakamura R, Maeda N, Shibata K, Yamada H, Kase T, Yoshikai Y. Interleukin-15 is critical in the pathogenesis of influenza a virus-induced acute lung injury. J Virol. 2010;84:5574-82 pubmed publisher..These results indicate that IL-15-dependent CD8(+) T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus. ..
- Yoshihara K, Yajima T, Kubo C, Yoshikai Y. Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice. Gut. 2006;55:334-41 pubmed..05). IL-15 plays an important role in the pathogenesis of both acute and chronic colitis induced by DSS in mice. ..
- Davey G, Starr R, Cornish A, Burghardt J, Alexander W, Carbone F, et al. SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential. J Exp Med. 2005;202:1099-108 pubmed..Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell-mediated disease of SOCS-1-/- mice. ..
- Nishimura H, Yajima T, Naiki Y, Tsunobuchi H, Umemura M, Itano K, et al. Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo. J Exp Med. 2000;191:157-70 pubmed..Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo. ..
- Nishimura H, Washizu J, Nakamura N, Enomoto A, Yoshikai Y. Translational efficiency is up-regulated by alternative exon in murine IL-15 mRNA. J Immunol. 1998;160:936-42 pubmed..These results suggest that normal IL-15 production in stimulated macrophages is regulated by splicing of alternative exon 5. ..
- Mitchell D, Ravkov E, Williams M. Distinct roles for IL-2 and IL-15 in the differentiation and survival of CD8+ effector and memory T cells. J Immunol. 2010;184:6719-30 pubmed publisher..These findings indicate a unique role for IL-2, but not IL-15, in promoting the differentiation not only of primary effector CD8+ T cells, but also of CD8+ memory T cells capable of secondary effector differentiation...
- Quinn L, Strait Bodey L, Anderson B, Argiles J, Havel P. Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes: evidence for a skeletal muscle-to-fat signaling pathway. Cell Biol Int. 2005;29:449-57 pubmed..These findings provide support for the hypothesis that IL-15 functions in a muscle-to-fat endocrine axis which modulates fat:lean body composition and insulin sensitivity. ..
- Joshi N, Cui W, Chandele A, Lee H, Urso D, Hagman J, et al. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity. 2007;27:281-95 pubmed..These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential. ..
- Mirghomizadeh F, Bullwinkel J, Orinska Z, Janssen O, Petersen A, Singh P, et al. Transcriptional regulation of mouse mast cell protease-2 by interleukin-15. J Biol Chem. 2009;284:32635-41 pubmed publisher..This suggests a novel model of cytokine-controlled protease transcription: non-CpG methylation maintains a chromosomal domain in an "open" configuration that is permissive for gene expression. ..
- Bayer A, Lee J, de la Barrera A, Surh C, Malek T. A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells. J Immunol. 2008;181:225-34 pubmed..Collectively, these data indicate that IL-7R signaling contributes to Treg cell development and peripheral homeostasis. ..
- Goldrath A, Sivakumar P, Glaccum M, Kennedy M, Bevan M, Benoist C, et al. Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med. 2002;195:1515-22 pubmed..Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments. ..
- Oh S, Perera L, Terabe M, Ni L, Waldmann T, Berzofsky J. IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis. Proc Natl Acad Sci U S A. 2008;105:5201-6 pubmed publisher..These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency. ..
- Pistilli E, Bogdanovich S, Garton F, Yang N, Gulbin J, Conner J, et al. Loss of IL-15 receptor ? alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles. J Clin Invest. 2011;121:3120-32 pubmed publisher..Therefore, we propose that IL-15R? has a role in defining the phenotype of fast skeletal muscles in vivo. ..
- Stonier S, Ma L, Castillo E, Schluns K. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation. Blood. 2008;112:4546-54 pubmed publisher..The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis. ..
- Kobayashi H, Dubois S, Sato N, Sabzevari H, Sakai Y, Waldmann T, et al. Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood. 2005;105:721-7 pubmedb>Interleukin 15 (IL-15) is a critical factor for the proliferation and activation of natural killer (NK) and CD8 T cells...
- Stoklasek T, Schluns K, Lefrancois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol. 2006;177:6072-80 pubmed..These findings hold significant importance for the use of IL-15 as a potential adjuvant/therapeutic and inducer of homeostatic proliferation, without the necessity for prior immunodepletion. ..
- Rückert R, Brandt K, Ernst M, Marienfeld K, Csernok E, Metzler C, et al. Interleukin-15 stimulates macrophages to activate CD4+ T cells: a role in the pathogenesis of rheumatoid arthritis?. Immunology. 2009;126:63-73 pubmed publisher..In view of high serum and synovial levels of IL-15 in patients with RA, our data suggest the possibility that this excess IL-15 in RA may stimulate monocytes/MPhi to activate the characteristic autoreactive CD4(+) T cells in RA. ..
- Pulendran B, Dillon S, Joseph C, Curiel T, Banchereau J, Mohamadzadeh M. Dendritic cells generated in the presence of GM-CSF plus IL-15 prime potent CD8+ Tc1 responses in vivo. Eur J Immunol. 2004;34:66-73 pubmed..Together, these data suggest that IL-15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo. This suggests potential roles for these IL-15 DC cells in the immunotherapy of tumors and infectious diseases. ..
- Hanisch U, Lyons S, Prinz M, Nolte C, Weber J, Kettenmann H, et al. Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase activity. J Biol Chem. 1997;272:28853-60 pubmed..Microglial IL-15 could thus play a pivotal role in the CNS and may participate in certain CNS and neuroendocrine functions previously ascribed to IL-2. ..
- Tan J, Ernst B, Kieper W, LeRoy E, Sprent J, Surh C. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med. 2002;195:1523-32 pubmed..Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct. ..
- Nielsen A, Hojman P, Erikstrup C, Fischer C, Plomgaard P, Mounier R, et al. Association between interleukin-15 and obesity: interleukin-15 as a potential regulator of fat mass. J Clin Endocrinol Metab. 2008;93:4486-93 pubmed publisher..IL-15 overexpression in skeletal muscle of mice reduced trunk fat mass but not sc fat mass. Our results indicate that IL-15 may be a regulator of trunk fat mass. ..
- Gomez Nicola D, Valle Argos B, Nieto Sampedro M. Blockade of IL-15 activity inhibits microglial activation through the NFkappaB, p38, and ERK1/2 pathways, reducing cytokine and chemokine release. Glia. 2010;58:264-76 pubmed publisher..Modulating IL-15 activity opens the possibility of developing new strategies to control gliotic events upon inflammatory stimulation. ..
- Huang Y, Cheng S, Chueh S, Tsai Y, Liou N, Guo Y, et al. Effects of interleukin-15 on neuronal differentiation of neural stem cells. Brain Res. 2009;1304:38-48 pubmed publisher..This signal transduction modifies MAP-2 protein levels and, consequently, the differentiation of neurons from NSCs, as evidenced by reduced neurite outgrowth. ..
- Becker T, Wherry E, Boone D, Murali Krishna K, Antia R, Ma A, et al. Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med. 2002;195:1541-8 pubmed..Taken together, these results show that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time. ..
- Dubois S, Waldmann T, Müller J. ITK and IL-15 support two distinct subsets of CD8+ T cells. Proc Natl Acad Sci U S A. 2006;103:12075-80 pubmed..Thus, whereas ITK-dependent CD44(lo)CD122(lo) CD8(+) T cells appear to represent conventional CD8(+) T cells, IL-15-dependent CD44(hi)CD122(hi) CD8(+) T cells may have functions in both adaptive and innate immunity. ..
- Umehara T, Udagawa J, Takamura K, Kimura M, Ishimitsu R, Kiyono H, et al. Role of interleukin-15 in the development of mouse olfactory nerve. Congenit Anom (Kyoto). 2009;49:253-7 pubmed publisher..Adult IL-15R alpha knockout mice had fewer mature olfactory neurons and proliferating cells than wild-type. Our results suggest that IL-15 plays an important role in regulating cell proliferation in olfactory neurogenesis. ..
- Khan I, Moretto M, Wei X, Williams M, Schwartzman J, Liew F. Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response. J Exp Med. 2002;195:1463-70 pubmed..gondii challenge. To our knowledge, this is the first demonstration of the important role of host IL-15 in the development of antigen-specific memory CD8+ T cells against an intracellular infection. ..
- Sandau M, Winstead C, Jameson S. IL-15 is required for sustained lymphopenia-driven proliferation and accumulation of CD8 T cells. J Immunol. 2007;179:120-5 pubmed..These findings demonstrate that cytokine requirements for LIP change during the process itself, illustrating the need to identify factors that regulate successive stages of lymphopenia-driven proliferation. ..
- Huang Z, Ha G, Petitto J. IL-15 and IL-15R alpha gene deletion: effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy. Neurosci Lett. 2007;417:160-4 pubmed..Further studies are needed to dissect the mechanisms that underlie these observations (e.g., central vs. peripheral immune contributions). ..
- Ranson T, Vosshenrich C, Corcuff E, Richard O, Laloux V, Lehuen A, et al. IL-15 availability conditions homeostasis of peripheral natural killer T cells. Proc Natl Acad Sci U S A. 2003;100:2663-8 pubmed..In contrast, TCR "tickling" of NK-T cells, if it occurs under steady-state conditions, does not by itself provide a sufficient signal for their peripheral survival. ..
- Li M, Sanjabi S, Flavell R. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity. 2006;25:455-71 pubmed..This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo. ..
- Vang K, Yang J, Mahmud S, Burchill M, Vegoe A, Farrar M. IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J Immunol. 2008;181:3285-90 pubmed
- de Totero D, Meazza R, Capaia M, Fabbi M, Azzarone B, Balleari E, et al. The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways. Blood. 2008;111:517-24 pubmed..The knowledge of the signaling pathways regulating CLL cell survival and proliferation may provide new molecular targets for therapeutic intervention. ..
- Castillo E, Stonier S, Frasca L, Schluns K. Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation. J Immunol. 2009;183:4948-56 pubmed publisher..Thus, an additional role for NK-DC interactions has been identified whereby DC support the developmental and homeostatic niche of NK cells. ..
- Zeng R, Spolski R, Finkelstein S, Oh S, Kovanen P, Hinrichs C, et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J Exp Med. 2005;201:139-48 pubmed..Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15. ..
- Giri J, Anderson D, Kumaki S, Park L, Grabstein K, Cosman D. IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2. J Leukoc Biol. 1995;57:763-6 pubmedb>Interleukin 15 is a newly discovered cytokine that shares biological activities with IL-2 and, like IL-2, is a member of the four-helix bundle cytokine family...
- Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med. 2012;209:2351-65 pubmed publisher..Moreover, our results reveal an essential role of CD4+ T cell help for sustained antitumor activity by NK cells linking adaptive and innate immunity. ..
- Tsunobuchi H, Nishimura H, Goshima F, Daikoku T, Suzuki H, Nakashima I, et al. A protective role of interleukin-15 in a mouse model for systemic infection with herpes simplex virus. Virology. 2000;275:57-66 pubmed..Taken together, these results suggest that IL-15, using the IL-2/IL15R beta chain, plays an important role in mounting protective immunity during the course of systemic HSV-2 infection. ..
- Mortier E, Woo T, Advincula R, Gozalo S, Ma A. IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med. 2008;205:1213-25 pubmed publisher..These studies define an unprecedented cytokine-receptor biosynthetic pathway in which IL-15Ralpha serves as a chaperone for IL-15, after which membrane-bound IL-15Ralpha-IL-15 complexes activate NK cells via direct cell-cell contact. ..