Research Topics
| Richard LocksleySummaryAffiliation: University of California Country: USA Publications
Research Grants
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Detail Information
Publications
CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage commitmentHelene Bour-Jordan
UCSF Diabetes Center and Department of Medicine, University of California San Francisco, 94143, USA
Nat Immunol 4:182-8. 2003..These results suggest that CTLA-4 has a critical role in T cell differentiation and that STAT6-dependent T(H)2 lineage commitment and stabilization can be bypassed by increasing the strength of signaling through the T cell receptor...
Raggin' on T-betRichard M Locksley
HHMI and Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 0795, USA Electronic address
Cell Metab 17:473-4. 2013..2013) report in this issue that mice deficient in the T-box transcription factor, T-bet, display a dissociated phenotype with enhanced perigonadal adipose but enhanced insulin sensitivity...
Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and diseaseSteven J Van Dyken
Departments of Medicine and Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA
Annu Rev Immunol 31:317-43. 2013....- Efficient generation of long-distance conditional alleles using recombineering and a dual selection strategy in replicate platesDavid Voehringer
Howard Hughes Medical Institute, Department of Medicine, University of California San Francisco, San Francisco, CA 94143 0795, USA
BMC Biotechnol 9:69. 2009..Therefore, we developed a new strategy to rapidly identify ES cells containing the desired allele... - Susceptibility to infectious diseases: Leishmania as a paradigmR M Locksley
Howard Hughes Medical Institute, University of California, San Francisco 94143 0654, USA
J Infect Dis 179:S305-8. 1999..Similar paradigms could underlie susceptibility to other pathogenic organisms... - The Roaring TwentiesRichard M Locksley
Howard Hughes Medical Institute, Department of Medicine and Microbiology Immunology, University of California, San Francisco, CA 94143, USA
Immunity 28:437-9. 2008..New cell types and cytokines have emerged as key participants in the elaboration of and recovery from inflammation. A collection of reviews covers recent advances in our understanding of this crucial component of host defense... - Nine lives: plasticity among T helper cell subsetsRichard M Locksley
Department of Medicine, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA
J Exp Med 206:1643-6. 2009..A deeper molecular context will be required to reconcile the ever-increasing complexity of effector T cells... - Asthma and allergic inflammationRichard M Locksley
Howard Hughes Medical Institute, University of California at San Francisco, 94143, USA
Cell 140:777-83. 2010..The similarities of these responses with mucosal responses to parasitic intestinal worms may reveal pathways relevant to the perplexing rise of these chronic inflammatory disorders... - Stat signals release activated naive Th cells from an anergic checkpointMarkus Mohrs
Howard Hughes Medical Institute and Department of Medicine, University of California-San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0654, USA
J Immunol 170:1870-6. 2003.... - T helper cell differentiation: on again, off againJane L Grogan
Howard Hughes Medical Institute, University of California San Francisco, 521 Parnassus Avenue, C 443, San Francisco, CA 94143 0654, USA
Curr Opin Immunol 14:366-72. 2002.... - Basal chromatin modification at the IL-4 gene in helper T cellsJane L Grogan
Howard Hughes Medical Institute, Department of Medicine and Microbiology Immunology, University of California, San Francisco, CA 94143 0654, USA
J Immunol 171:6672-9. 2003..Hyperacetylation of nonexpressed genes may serve to mark lineage-specific loci for rapid expression and further modification... - Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivoJennifer L Matsuda
La Jolla Institute for Allergy and Immunology, and Division of Biological Sciences, University of California, San Diego, CA, USA
Proc Natl Acad Sci U S A 100:8395-400. 2003.... - Th2 cells: orchestrating barrier immunityDaniel B Stetson
Howard Hughes Medical Institute, University of California San Francisco, 94143, USA
Adv Immunol 83:163-89. 2004 - Systemically dispersed innate IL-13-expressing cells in type 2 immunityApril E Price
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, CA 94143 0795, USA
Proc Natl Acad Sci U S A 107:11489-94. 2010..Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses... - Helper T cells regulate type-2 innate immunity in vivoKanade Shinkai
Howard Hughes Medical Institute, Department of Medicine and Microbiology, University of California San Francisco, 94143-0654, USA
Nature 420:825-9. 2002..Helper T cells confer antigen specificity on eosinophil cytotoxicity, but not cytokine responses, so defining a novel mechanism that focuses tissue injury at sites of immune challenge... - T helper cell effector fates--who, how and where?R Lee Reinhardt
University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0795, USA
Curr Opin Immunol 18:271-7. 2006..Finally, the role of innate cells in influencing these processes has become increasingly realized... - Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 productionDavid Voehringer
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA
Immunity 20:267-77. 2004..Primary type 2 immune responses in the lung represent the focal recruitment and activation of discrete cell populations from the blood that have previously committed to express IL-4... - Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophagesDavid Voehringer
Howard Hughes Medical Institute, Department of Medicine, University of California San Francisco, San Francisco, California, USA
J Leukoc Biol 81:1434-44. 2007..Alternatively activated macrophages contributed substantially to tissue recruitment of eosinophils, providing a novel basis for development of therapeutic approaches to lower tissue eosinophilia... - Lung CD25 CD4 regulatory T cells suppress type 2 immune responses but not bronchial hyperreactivityHusein Hadeiba
Department of Medicine, University of California, San Francisco, CA 94143, USA
J Immunol 170:5502-10. 2003..Despite their ability to suppress allergic type 2 immunity in the airways, however, CD25(+) CD4 regulatory T cells had no effect on the development of bronchial hyperreactivity... - Normal development and activation but altered cytokine production of Fyn-deficient CD4+ T cellsAlusha A Mamchak
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
J Immunol 181:5374-85. 2008..These data demonstrate that ablation of Fyn expression does not alter most Ag-driven CD4(+) T cell responses, with the exception of cytokine production, which under some circumstances is enhanced in Fyn-deficient CD4(+) T cells... - Cytokine-secreting follicular T cells shape the antibody repertoireR Lee Reinhardt
Howard Hughes Medical Institute and Departments of Medicine and Microbiology and Immunology, University of California San Francisco, USA
Nat Immunol 10:385-93. 2009..Our findings support a model in which B cells compete for cytokines produced by follicular helper T cells that shape the affinity and isotype of the antibody response... - IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathwayKelly M Kroeger
Howard Hughes Medical Institute, Departments of Medicine and Microbiology Immunology, University of California San Francisco, San Francisco, California, USA
J Leukoc Biol 86:769-78. 2009..In addition, basophil survival increased in the presence of IL-18 or IL-33 as a result of increased Akt activation. Studies in vivo confirmed the potency of IL-18 and IL-33 in activating cytokine release from mouse basophils... - Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells in vivoDaniel B Stetson
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, 94143, USA
Immunity 17:191-200. 2002..CD4 subset polarization in this highly characterized model occurs independently from IL-4 expression by naive T cells, which is activated indiscriminately after parasitism... - Visualization of IL-12/23p40 in vivo reveals immunostimulatory dendritic cell migrants that promote Th1 differentiationR Lee Reinhardt
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, CA 94143, USA
J Immunol 177:1618-27. 2006.... - Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic miceQizhi Tang
Diabetes Center, Department of Medicine, University of California, San Francisco 94143, USA
Nat Immunol 7:83-92. 2006..Such persistent T(reg) cell-dendritic cell contacts preceded the inhibition of T(H) cell activation by dendritic cells, supporting the idea that dendritic cells are central to T(reg) cell function in vivo... - Activation of the integrated stress response during T helper cell differentiationStefanie Scheu
Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA
Nat Immunol 7:644-51. 2006..Therefore, T lymphocytes require components of the integrated stress response to uncouple differentiation from the execution of effector functions... - A failure to launch: fuelling cytokine secretion in iNKT cellsRichard M Locksley
Howard Hughes Medical Institute, Department of Medicine and Microbiology/Immunology, University of California, San Francisco, San Francisco, California 94143-0795, USA
Immunity 25:393-5. 2006..2006) uncover an unsuspected role for the cytokine GM-CSF in the thymic development of invariant NKT cells, a role that licenses these cells to secrete effector cytokines upon activation in the periphery... - Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector functionDaniel B Stetson
University of California San Francisco, Box 0654, C 443, 521 Parnassus Avenue, San Francisco, CA 94143, USA
J Exp Med 198:1069-76. 2003..Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes... - Innate immune responses in peptidoglycan recognition protein L-deficient miceMin Xu
Howard Hughes Medical Institute, Department of Medicine, University of California San Francisco, 94143 0654, USA
Mol Cell Biol 24:7949-57. 2004..In contrast to its critical role in immunity in flies, PGRP-L is largely dispensable for mammalian immunity against bacteria and fungi... - The Leishmania major LACK antigen with an immunodominant epitope at amino acids 156 to 173 is not required for early Th2 development in BALB/c miceBen L Kelly
Departmrnt of Medicine, Howard Hughes Medical Institute, University of California-San Francisco, UCSF Medical Center, Room C-443, 521 Parnassus Avenue, San Francisco, CA 94143-0654, USA
Infect Immun 72:6924-31. 2004..Mice inoculated with mutant parasites were not protected against subsequent infection with wild-type L. major... - Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infectionP ng Loke
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA
Proc Natl Acad Sci U S A 102:9872-7. 2005..The primary role of ICOS in a chronic helminth infection could be to drive antibodies toward type 2 isotypes. T-independent antibody response to the parasite could be enhanced in the absence of costimulation and T cell help... - Differential enzymatic activity of common haplotypic versions of the human acidic Mammalian chitinase proteinMax A Seibold
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA
J Biol Chem 284:19650-8. 2009..The structural, kinetic, and genetic data regarding the AMCase isoforms are consistent with the Th2-priming effects of environmental chitin and a role for AMCase in negatively regulating this stimulus... - Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune systemDavid Voehringer
Howard Hughes Medical Institute, Departments of Medicine and Microbiology Immunology, University of California San Francisco, San Francisco, CA 94143, USA
J Exp Med 203:1435-46. 2006..Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell-dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity... - Nippostrongylus brasiliensis: identification of intelectin-1 and -2 as Stat6-dependent genes expressed in lung and intestine during infectionDavid Voehringer
Department of Medicine and Microbiology, University of California San Francisco, San Francisco, CA 94143, USA
Exp Parasitol 116:458-66. 2007..Further, no significant modulation of the immune response in lung or lymph nodes was observed. Thus, under these conditions, intelectins did not enhance pathogen clearance... - Rapid IL-4 production by Leishmania homolog of mammalian RACK1-reactive CD4(+) T cells in resistant mice treated once with anti-IL-12 or -IFN-gamma antibodies at the onset of infection with Leishmania major instructs Th2 cell development, resulting in nonPascal Launois
World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Lausanne, Switzerland
J Immunol 168:4628-35. 2002..Together these results suggest that a deficiency in mechanisms capable of down-regulating the early IL-4 response to L. major contributes to the exquisite susceptibility of BALB/c mice to L. major... - TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cellsMarc Veldhoen
Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
Immunity 24:179-89. 2006..Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells... - Replication initiation from a novel origin identified in the Th2 cytokine cluster locus requires a distant conserved noncoding sequenceToshiro Hayashida
Cytokine Project, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, 113-8613 Tokyo, Japan
J Immunol 176:5446-54. 2006.... - LACK-reactive CD4+ T cells require autocrine IL-2 to mediate susceptibility to Leishmania majorAlain Gumy
World Health Organization Immunology Research and Training Centre, University of Lausanne, Epalinges, Switzerland
Eur J Immunol 36:1465-73. 2006..Thus, in C57BL/6 mice, the inability of LACK-reactive CD4(+) T cells to express early IL-4 mRNA transcription, important for disease progression, appears due to an incapacity of these cells to produce IL-2... - Interleukin-4 can be a key positive regulator of inflammatory arthritisKoichiro Ohmura
Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Arthritis Rheum 52:1866-75. 2005..The potential of IL-4 to promote inflammatory arthritis should be considered when proposing therapies for rheumatoid arthritis aimed at biasing T cells toward IL-4 production... - IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challengeShabaana A Khader
Trudeau Institute, Saranac Lake, New York 12983, USA
Nat Immunol 8:369-77. 2007.... - Regulation of homeostatic chemokine expression and cell trafficking during immune responsesScott N Mueller
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Science 317:670-4. 2007..We propose that this transient chemokine modulation may help orchestrate local cellularity, thus minimizing competition for space and resources in activated lymphoid tissues... - A two-step process for cytokine production revealed by IL-4 dual-reporter miceKatja Mohrs
Trudeau Institute, Saranac Lake, New York 12983, USA
Immunity 23:419-29. 2005..These data reveal a two-step process for cytokine production: the first generating poised cells that disseminate systemically and the second inducing the rapid production of the cytokine in response to local stimulation... - Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gammaKirk D C Jensen
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
Immunity 29:90-100. 2008..The swift IL-17 response mounted by antigen-naive gammadelta T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens...
Research Grants
- HELPER T CELL SUBSETS IN LEISHMANIASISRichard Locksley; Fiscal Year: 2000..major such that human homologs might be found. ..
- CD4+ T CELL RECEPTORS IN LEISHMANIASISRichard Locksley; Fiscal Year: 2002..Further, targeting this pool by either understanding its fine specificity or the requirements for Th development can overcome genetic tendencies and provide protection from otherwise fatal infection. ..
- Initiation of allergic immunity by parasitesRichard Locksley; Fiscal Year: 2009..PUBLIC HEALTH RELEVANCE: Helminths infect over 2.9 billion humans and are estimated to cause morbidity approaching those of diabetes and lung cancer. New insights regarding the pathogenesis of these infections are greatly needed. ..
- Parasite Immunity Orchestrated by Th2 CellsRichard Locksley; Fiscal Year: 2007....
- CD4+ T CELL RECEPTORS IN LEISHMANIASISRichard Locksley; Fiscal Year: 2007..abstract_text> ..
- CD4+ T CELL RECEPTORS IN LEISHMANIASISRichard Locksley; Fiscal Year: 2006..abstract_text> ..
- HELPER T CELL SUBSETS IN LEISHMANIASISRichard Locksley; Fiscal Year: 2005..The use of a parasite model in which the outcome has been so clearly tied to this decision offers an opportunity for important insights into disease susceptibility and effective vaccine strategy. ..
- CD4+ T CELL RECEPTORS IN LEISHMANIASISRichard Locksley; Fiscal Year: 1993....
- HELPER T CELL SUBSETS IN LEISHMANIASISRichard Locksley; Fiscal Year: 1993..These studies should provide important insights towards the understanding of Th1 and Th2 cell subset maturation and the characteristics of critical parasite antigens involved in this process...
- HELPER T CELL SUBSETS IN LEISHMANIASISRichard Locksley; Fiscal Year: 1991..The long term goal will be to use these discrete populations of cloned T cells to screen Leishmania antigens that could function as candidate vaccines or that mediate the immunosuppression of progressive disease...
- Initiation of allergic immunity by parasitesRichard M Locksley; Fiscal Year: 2010..PUBLIC HEALTH RELEVANCE: Helminths infect over 2.9 billion humans and are estimated to cause morbidity approaching those of diabetes and lung cancer. New insights regarding the pathogenesis of these infections are greatly needed. ..