Genomes and Genes
Gene Symbol: Rag1
Description: recombination activating gene 1
Alias: Rag-1, V(D)J recombination-activating protein 1, recombinase activating gene 1, recombination activating protein 1
- Jin J, Yu Q. Systemic administration of TLR3 agonist induces IL-7 expression and IL-7-dependent CXCR3 ligand production in the lung. J Leukoc Biol. 2013;93:413-25 pubmed publisher..In a model of multiorgan inflammation elicited by adoptive transfer of immune cells into RAG1(-/-) mice, we show that poly I:C enhances IL-7 production in the lung and promotes expression of CXCR3 ligands and ..
- Withers D, Gaspal F, Mackley E, Marriott C, Ross E, Desanti G, et al. Cutting edge: lymphoid tissue inducer cells maintain memory CD4 T cells within secondary lymphoid tissue. J Immunol. 2012;189:2094-8 pubmed publisher..These data demonstrate a novel role for LTi cells, archetypal members of the innate lymphoid cell family, in supporting memory CD4 T cell survival in vivo. ..
- Naik S, Bouladoux N, Wilhelm C, Molloy M, Salcedo R, Kastenmuller W, et al. Compartmentalized control of skin immunity by resident commensals. Science. 2012;337:1115-9 pubmed publisher..These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease. ..
- Ouyang W, Liao W, Luo C, Yin N, Huse M, Kim M, et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012;491:554-9 pubmed publisher..These findings show that the evolutionarily ancient Akt-Foxo1 signalling module controls a novel genetic program indispensable for T(reg) cell function. ..
- Ramalingam R, Larmonier C, Thurston R, Midura Kiela M, Zheng S, Ghishan F, et al. Dendritic cell-specific disruption of TGF-? receptor II leads to altered regulatory T cell phenotype and spontaneous multiorgan autoimmunity. J Immunol. 2012;189:3878-93 pubmed publisher..Therefore, in vivo, TGF-? signaling in DCs is critical in the control of autoimmunity through both Treg-dependent and -independent mechanisms, but it does not affect MHCII and costimulatory molecule expression. ..
- Cuda C, Wan S, Sobel E, Croker B, Morel L. Murine lupus susceptibility locus Sle1a controls regulatory T cell number and function through multiple mechanisms. J Immunol. 2007;179:7439-47 pubmed..Overall, these results show that Sle1a controls both Treg number and function by multiple mechanisms, directly on the Tregs themselves and indirectly through the response of effector T cells and the regulatory role of dendritic cells. ..
- Maraskovsky E, O Reilly L, Teepe M, Corcoran L, Peschon J, Strasser A. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell. 1997;89:1011-9 pubmed..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2. ..
- Difilippantonio S, Gapud E, Wong N, Huang C, Mahowald G, Chen H, et al. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature. 2008;456:529-33 pubmed publisher..These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks. ..
- Pape K, Taylor J, Maul R, Gearhart P, Jenkins M. Different B cell populations mediate early and late memory during an endogenous immune response. Science. 2011;331:1203-7 pubmed publisher..Thus, we propose that memory relies on swIg(+) cells until they disappear and serum immunoglobulin falls to a low level, in which case memory resides with durable IgM(+) reserves. ..
- Zhang X, Chen W, de Paiva C, Volpe E, Gandhi N, Farley W, et al. Desiccating stress induces CD4+ T-cell-mediated Sjögren's syndrome-like corneal epithelial apoptosis via activation of the extrinsic apoptotic pathway by interferon-?. Am J Pathol. 2011;179:1807-14 pubmed publisher..CD4(+) T-cell-produced IFN-? plays a pivotal role in DS-induced corneal epithelial apoptosis via activation of the extrinsic apoptotic pathway. ..
- Owyang A, Zaph C, Wilson E, Guild K, McClanahan T, Miller H, et al. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med. 2006;203:843-9 pubmed..Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract...
- Wang C, Kang S, Lee J, Sun Z, Kim C. The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut. Mucosal Immunol. 2009;2:173-83 pubmed publisher..We conclude that CCR6 regulates Th17 cell migration to the gut and effector T-cell balance/distribution in inflamed intestine. ..
- Borghesi L, Hsu L, Miller J, Anderson M, Herzenberg L, Herzenberg L, et al. B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors. J Exp Med. 2004;199:491-502 pubmed..As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors. ..
- DiLorenzo T, Lieberman S, Takaki T, Honda S, Chapman H, Santamaria P, et al. During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities. Clin Immunol. 2002;105:332-41 pubmed..NIT-1 cells represent an unlimited peptide source that will allow for the future isolation and sequencing of the novel multiple epitopes targeted early in the autoimmune response by pathogenic CD8(+) T cells. ..
- Oettinger M, Schatz D, Gorka C, Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990;248:1517-23 pubmed..RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction. ..
- Ahern P, Schiering C, Buonocore S, McGeachy M, Cua D, Maloy K, et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity. 2010;33:279-88 pubmed publisher..Together, these results highlight the multiple functions of IL-23 signaling in T cells that contribute to its colitogenic activity. ..
- Mombaerts P, Iacomini J, Johnson R, Herrup K, Tonegawa S, Papaioannou V. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68:869-77 pubmed..Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice. ..
- Godfrey D, Kennedy J, Mombaerts P, Tonegawa S, Zlotnik A. Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation. J Immunol. 1994;152:4783-92 pubmed
- Fugmann S, Villey I, Ptaszek L, Schatz D. Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex. Mol Cell. 2000;5:97-107 pubmedDuring V(D)J recombination, the RAG1 and RAG2 proteins cooperate to catalyze a series of DNA bond breakage and strand transfer reactions...
- Nagahama K, Ogawa A, Shirane K, Shimomura Y, Sugimoto K, Mizoguchi A. Protein kinase C theta plays a fundamental role in different types of chronic colitis. Gastroenterology. 2008;134:459-69 pubmed..PKCtheta serves as a common and fundamental signaling molecule in the development of different types of colitis and may represent an attractive target for treating inflammatory bowel disease. ..
- Cobbold S, Castejon R, Adams E, Zelenika D, Graca L, Humm S, et al. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J Immunol. 2004;172:6003-10 pubmed..These data suggest that regulatory T cells maintaining transplantation tolerance after CD4 Ab blockade can be induced de novo through a TGF-beta-dependent mechanism, and come to accumulate in tolerated grafts. ..
- Wensky A, Furtado G, Marcondes M, Chen S, Manfra D, Lira S, et al. IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis. J Immunol. 2005;174:1416-23 pubmed
- Mansson R, Zandi S, Welinder E, Tsapogas P, Sakaguchi N, Bryder D, et al. Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity. Blood. 2010;115:2601-9 pubmed publisher..events involved in the regulation of lymphoid lineage commitment, we crossed lambda5 reporter transgenic mice to Rag1-GFP knockin mice...
- Polic B, Kunkel D, Scheffold A, Rajewsky K. How alpha beta T cells deal with induced TCR alpha ablation. Proc Natl Acad Sci U S A. 2001;98:8744-9 pubmed
- Siggs O, Arnold C, Huber C, Pirie E, Xia Y, Lin P, et al. The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow. Nat Immunol. 2011;12:434-40 pubmed publisher..Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development. ..
- Schwarz K, Gauss G, Ludwig L, Pannicke U, Li Z, Lindner D, et al. RAG mutations in human B cell-negative SCID. Science. 1996;274:97-9 pubmed..Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both...
- Bajou K, Peng H, Laug W, Maillard C, Noel A, Foidart J, et al. Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell. 2008;14:324-34 pubmed publisher..We further demonstrate that plasmin cleaves FasL at Arg144-Lys145, releasing a soluble proapoptotic FasL fragment from the surface of ECs. The data provide a mechanism explaining the proangiogenic activity of PAI-1. ..
- King C, Kobayashi T, Cejas P, Kim T, Yoon K, Kim G, et al. TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis. Nat Med. 2006;12:1088-92 pubmed..These data identify a previously unrecognized role for TRAF6 in the maintenance of peripheral tolerance, and suggest the presence of a T cell-intrinsic control mechanism to render responder T cells susceptible to tolerizing signals. ..
- Nicolson K, O Neill E, Sundstedt A, Streeter H, Minaee S, Wraith D. Antigen-induced IL-10+ regulatory T cells are independent of CD25+ regulatory cells for their growth, differentiation, and function. J Immunol. 2006;176:5329-37 pubmed..These results demonstrate that these natural and induced regulatory cells fall into distinct subsets. ..
- Aurora A, Baluk P, Zhang D, Sidhu S, Dolganov G, Basbaum C, et al. Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infection. J Immunol. 2005;175:6319-26 pubmed..The results reveal a novel pathway whereby T cell-dependent humoral immunity to a persistent airway infection can induce inflammation-dependent angiogenesis, lymphangiogenesis, and chronic airway pathology...
- Bettelli E, Pagany M, Weiner H, Linington C, Sobel R, Kuchroo V. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med. 2003;197:1073-81 pubmed
- Ploquin M, Eksmond U, Kassiotis G. B cells and TCR avidity determine distinct functions of CD4+ T cells in retroviral infection. J Immunol. 2011;187:3321-30 pubmed publisher..Our results suggest that B cell presentation of vaccine Ags could be manipulated to direct the appropriate CD4(+) T cell response...
- Bour Jordan H, Salomon B, Thompson H, Szot G, Bernhard M, Bluestone J. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J Clin Invest. 2004;114:979-87 pubmed..Thus, elimination of Treg's results in diabetes even in the absence of costimulation, which suggests a need for alternative strategies for immunotherapeutic approaches. ..
- Yamazaki T, Yang X, Chung Y, Fukunaga A, Nurieva R, Pappu B, et al. CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol. 2008;181:8391-401 pubmed..Similarly, CCR6 on Treg cells is also important for their recruitment into inflammatory tissues. Our data indicate an important role of CCR6 in Treg and Th17 cell migration. ..
- Gutcher I, Donkor M, Ma Q, Rudensky A, Flavell R, Li M. Autocrine transforming growth factor-?1 promotes in vivo Th17 cell differentiation. Immunity. 2011;34:396-408 pubmed publisher..These findings reveal an essential role for activated T cell-produced TGF-?1 in promoting the differentiation of Th17 cells and controlling inflammatory diseases. ..
- Ngo V, Korner H, Gunn M, Schmidt K, Riminton D, Cooper M, et al. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med. 1999;189:403-12 pubmed..Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen. ..
- Laouar Y, Town T, Jeng D, Tran E, WAN Y, Kuchroo V, et al. TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2008;105:10865-70 pubmed publisher..Our data provide direct evidence that TGF-beta can control autoimmunity via actions on DCs. ..
- Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz D. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell. 2010;141:419-31 pubmed publisherThe critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo...
- Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15:921-9 pubmed publisher..CD4(+) (but not CD8(+)) T cell transfer into lymphocyte-free Rag1-null DIO mice reversed weight gain and insulin resistance, predominantly through T(H)2 cells...
- Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel R, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol. 2008;9:1347-55 pubmed publisher..Thus IL-9(+)IL-10(+) T cells lack suppressive function and constitute a distinct population of helper-effector T cells that promote tissue inflammation. ..
- Samuelsson C, Hausmann J, Lauterbach H, Schmidt M, Akira S, Wagner H, et al. Survival of lethal poxvirus infection in mice depends on TLR9, and therapeutic vaccination provides protection. J Clin Invest. 2008;118:1776-84 pubmed publisher..Therefore, these data suggest an essential role for TLR9 in the defense against poxviruses. In addition, postexposure application of MVA may protect against lethal poxvirus infection...
- Wu Q, Wang Y, Wang J, Hedgeman E, Browning J, Fu Y. The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues. J Exp Med. 1999;190:629-38 pubmed..Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues. ..
- Prisco A, Vanes L, Ruf S, Trigueros C, Tybulewicz V. Lineage-specific requirement for the PH domain of Vav1 in the activation of CD4+ but not CD8+ T cells. Immunity. 2005;23:263-74 pubmed..Unexpectedly, the mutation selectively affects TCR-induced proliferation of CD4(+) but not CD8(+) T cells, demonstrating differences in the wiring of TCR signaling pathways between the two lineages. ..
- Hsieh C, Zheng Y, Liang Y, Fontenot J, Rudensky A. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol. 2006;7:401-10 pubmed..Our analyses suggest that T(reg) cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs. ..
- Kassiotis G, Garcia S, Simpson E, Stockinger B. Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nat Immunol. 2002;3:244-50 pubmed..Thus, in contrast to their survival, maintenance of the typical quality of memory T cells crucially depends on MHC-derived signals. ..
- Brickshawana A, Shapiro V, Kita H, Pease L. Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow. J Immunol. 2011;187:5795-804 pubmed publisher..IL-33 cultures of bone marrow cells from Rag1 KO and Kit(W-sh/W-sh) mice also responded similarly; hence, eliminating the possible contributions of T, B, and ..
- Erazo A, Kutchukhidze N, Leung M, Christ A, Urban J, Curotto de Lafaille M, et al. Unique maturation program of the IgE response in vivo. Immunity. 2007;26:191-203 pubmed..Our results have implications for the understanding of IgE memory responses in allergy. ..
- Yu W, Nagaoka H, Jankovic M, Misulovin Z, Suh H, Rolink A, et al. Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization. Nature. 1999;400:682-7 pubmed..Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance. ..
- Welner R, Esplin B, Garrett K, Pelayo R, Luche H, Fehling H, et al. Asynchronous RAG-1 expression during B lymphopoiesis. J Immunol. 2009;183:7768-77 pubmed publisher..Other progenitors first activate this locus after c-Kit levels have diminished and cell surface IL-7 receptors are detectable. ..
- Amin R, Schlissel M. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat Immunol. 2008;9:613-22 pubmed publisher..Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease in Foxo1 protein diminished the induction of Rag1 ..
- Pillai M, Collison L, Wang X, Finkelstein D, Rehg J, Boyd K, et al. The plasticity of regulatory T cell function. J Immunol. 2011;187:4987-97 pubmed publisher..These data reveal that cross-regulatory pathways exist that control the utilization of suppressive mechanisms, thereby providing T(reg) functional plasticity. ..
- McGargill M, Mayerova D, Stefanski H, Koehn B, Parke E, Jameson S, et al. A spontaneous CD8 T cell-dependent autoimmune disease to an antigen expressed under the human keratin 14 promoter. J Immunol. 2002;169:2141-7 pubmed..We discuss the potential relationship between autoimmunity and self-Ags that are expressed in stratified epithelium. ..
- Peak M, Arbuckle J, Rodgers K. The central domain of core RAG1 preferentially recognizes single-stranded recombination signal sequence heptamer. J Biol Chem. 2003;278:18235-40 pubmedb>RAG1 and RAG2 initiate V(D)J recombination by introducing DNA double strand breaks between each selected gene segment and its bordering recombination signal sequence (RSS) in a two-step mechanism in which the DNA is first nicked, followed ..
- Min B, Foucras G, Meier Schellersheim M, Paul W. Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoire. Proc Natl Acad Sci U S A. 2004;101:3874-9 pubmed..This finding suggests that the immune system has evolved mechanisms to attain a memory cell repertoire of great diversity independently of foreign antigens. ..
- Walzer T, Blery M, Chaix J, Fuseri N, Chasson L, Robbins S, et al. Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46. Proc Natl Acad Sci U S A. 2007;104:3384-9 pubmed..DT injection in these mice leads to a complete and selective NK cell ablation. This model paves a way for the in vivo characterization and preclinical assessment of NK cell biological function. ..
- Hewitt S, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, et al. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol. 2009;10:655-64 pubmed publisher..homologous immunoglobulin pairing was much lower in the absence of the RAG-1-RAG-2 recombinase and was restored in Rag1-/- developing B cells with a transgene expressing a RAG-1 active-site mutant that supported DNA binding but not ..
- Spanopoulou E, Cortes P, Shih C, Huang C, Silver D, Svec P, et al. Localization, interaction, and RNA binding properties of the V(D)J recombination-activating proteins RAG1 and RAG2. Immunity. 1995;3:715-26 pubmedThe RAG1 and RAG2 gene products are indispensable for activating somatic rearrangement of antigen receptor gene segments. The two proteins form a stable complex in primary thymocytes as well as when expressed in adherent cells...
- Bonnet M, Preukschat D, Welz P, Van Loo G, Ermolaeva M, Bloch W, et al. The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity. 2011;35:572-82 pubmed publisher..Collectively, our findings provide an in vivo experimental paradigm that regulation of necroptosis in keratinocytes is important for the maintenance of immune homeostasis and the prevention of chronic inflammation in the skin. ..
- Sekiguchi J, Whitlow S, Alt F. Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs. Mol Cell. 2001;8:1383-90 pubmedb>RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs...
- Curotto de Lafaille M, Muriglan S, Sunshine M, Lei Y, Kutchukhidze N, Furtado G, et al. Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes. J Exp Med. 2001;194:1349-59 pubmed..Our results indicate that hyper IgE responses do not occur in normal individuals due to the presence of regulatory T cells, and imply that the induction of regulatory CD4(+) T cells could be used for the prevention of atopy. ..
- Brien J, Uhrlaub J, Nikolich Zugich J. West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection. J Immunol. 2008;181:8568-75 pubmed..These results demonstrate the role of direct effector function of Ag-specific CD4 T cells in preventing severe WNV disease. ..
- Giblin W, Chatterji M, Westfield G, Masud T, Theisen B, Cheng H, et al. Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood. 2009;113:2965-75 pubmed publisherThe RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences...
- Garcia S, DiSanto J, Stockinger B. Following the development of a CD4 T cell response in vivo: from activation to memory formation. Immunity. 1999;11:163-71 pubmed..They differ qualitatively from naive T cells, suggesting that accelerated CD4 memory responses can occur without the need for increased frequencies of specific T cells. ..
- Pisitkun P, Deane J, Difilippantonio M, Tarasenko T, Satterthwaite A, Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006;312:1669-72 pubmed..These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation. ..
- Hotchkiss R, Swanson P, Knudson C, Chang K, Cobb J, Osborne D, et al. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol. 1999;162:4148-56 pubmed..We conclude that overexpression of Bcl-2 provides protection against cell death in sepsis. Lymphocyte death may be detrimental in sepsis by compromising host defense. ..
- Kuwata N, Igarashi H, Ohmura T, Aizawa S, Sakaguchi N. Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene. J Immunol. 1999;163:6355-9 pubmed..To study possible secondary B cell maturation, we prepared mice carrying a target integration of gfp gene into a rag1 locus (rag1/gfp mice). The GFP+ cells express rag1 mRNA and are undergoing Ig gene rearrangement...
- Miyao T, Floess S, Setoguchi R, Luche H, Fehling H, Waldmann H, et al. Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity. 2012;36:262-75 pubmed publisher..This study establishes that Treg cells constitute a stable cell lineage, whose committed state in a changing environment is ensured by DNA demethylation of the Foxp3 locus irrespectively of ongoing Foxp3 expression. ..
- Jones J, Gellert M. Ordered assembly of the V(D)J synaptic complex ensures accurate recombination. EMBO J. 2002;21:4162-71 pubmedRecombination of gene segments at the immunoglobulin and T-cell receptor loci requires that the RAG1 and RAG2 proteins bring together DNA signal sequences (RSSs) with 12- and 23-bp spacers into a synaptic complex and cleave the DNA...
- D Alessio F, Tsushima K, Aggarwal N, West E, Willett M, Britos M, et al. CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. J Clin Invest. 2009;119:2898-913 pubmed publisher..These results indicate that Tregs modify innate immune responses during resolution of lung injury and suggest potential targets for treating ALI, for which there are no specific therapies currently available...
- Kim K, Zhao J, Auh S, Yang X, Du P, Tang H, et al. Adaptive immune cells temper initial innate responses. Nat Med. 2007;13:1248-52 pubmed..Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. ..
- Igyarto B, Haley K, Ortner D, Bobr A, Gerami Nejad M, Edelson B, et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity. 2011;35:260-72 pubmed publisher..Langerin(+) dDCs also inhibited the ability of LCs and classic DCs to promote Th17 cell responses. This work demonstrates that skin-resident DC subsets promote distinct and opposing antigen-specific responses. ..
- Haks M, Krimpenfort P, van den Brakel J, Kruisbeek A. Pre-TCR signaling and inactivation of p53 induces crucial cell survival pathways in pre-T cells. Immunity. 1999;11:91-101 pubmed..In addition, the CD4+ CD8+ (DP) compartment is expanded to its normal size. These findings suggest that the pre-TCR regulates progression through the DNA-damage checkpoint of the DN to DP transition by inactivating p53. ..
- Schatz D, Oettinger M, Schlissel M. V(D)J recombination: molecular biology and regulation. Annu Rev Immunol. 1992;10:359-83 pubmed
- Takahashi Y, Inamine A, Hashimoto S, Haraguchi S, Yoshioka E, Kojima N, et al. Novel role of the Ras cascade in memory B cell response. Immunity. 2005;23:127-38 pubmed..Thus, our data suggest that upon antigen stimulation, memory B cells are susceptible to apoptosis but can be rescued via an antiapoptotic effect mediated through the Ras cascade. ..
- Xie Y, Akpinarli A, Maris C, Hipkiss E, Lane M, Kwon E, et al. Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J Exp Med. 2010;207:651-67 pubmed publisher..Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4(+) T cells...
- Sharma R, Deshmukh U, Zheng L, Fu S, Ju S. X-linked Foxp3 (Scurfy) mutation dominantly inhibits submandibular gland development and inflammation respectively through adaptive and innate immune mechanisms. J Immunol. 2009;183:3212-8 pubmed publisher..Fas(lpr/lpr) mice remained free of inflammation, even though their lymph node cells induced SMG inflammation in Rag1(-/-) recipients...
- Chung Y, Chang S, Martinez G, Yang X, Nurieva R, Kang H, et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity. 2009;30:576-87 pubmed publisher..Our data thus indicate a critical role of IL-1 in Th17 cell differentiation and this pathway may serve as a unique target for Th17 cell-mediated immunopathology. ..
- Corneo B, Wendland R, Deriano L, Cui X, Klein I, Wong S, et al. Rag mutations reveal robust alternative end joining. Nature. 2007;449:483-6 pubmed..mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient...
- Siggs O, Miosge L, Yates A, Kucharska E, Sheahan D, Brdicka T, et al. Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions. Immunity. 2007;27:912-26 pubmed..The pleiotropic functions of ZAP-70 and their differential response to graded variation provide a paradigm for understanding the complex outcomes of human genetic variation. ..
- Tsai C, Drejer A, Schatz D. Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination. Genes Dev. 2002;16:1934-49 pubmed..We have identified RAG1 mutants that are proficient in DNA cleavage but defective in their ability to interact with coding ends after ..
- Kim D, Dai Y, Mundy C, Yang W, Oettinger M. Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes Dev. 1999;13:3070-80 pubmedThe RAG1 and RAG2 proteins collaborate to initiate V(D)J recombination by binding recombination signal sequences (RSSs) and making a double-strand break between the RSS and adjacent coding DNA...
- Radulovic K, Manta C, Rossini V, Holzmann K, Kestler H, Wegenka U, et al. CD69 regulates type I IFN-induced tolerogenic signals to mucosal CD4 T cells that attenuate their colitogenic potential. J Immunol. 2012;188:2001-13 pubmed publisher..Hence, the activation Ag CD69 plays an important role in regulating mucosal immune responses. ..
- Deriano L, Chaumeil J, Coussens M, Multani A, Chou Y, Alekseyenko A, et al. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature. 2011;471:119-23 pubmed publisherMisrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice...