Now showing items 1-20 of 26

    • Defining the functional states of Th17 cells 

      Lee, Youjin; Kuchroo, Vijay (F1000Research, 2015)
      The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 Th cells ...
    • Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity 

      Paterson, Alison M.; Lovitch, Scott B.; Sage, Peter T.; Juneja, Vikram R.; Lee, Youjin; Trombley, Justin D.; Arancibia-Cárcamo, Carolina V.; Sobel, Raymond A.; Rudensky, Alexander Y.; Kuchroo, Vijay K.; Freeman, Gordon J.; Sharpe, Arlene H. (The Rockefeller University Press, 2015)
      Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate ...
    • The Dichotomous Pattern of IL-12R and IL-23R Expression Elucidates the Role of IL-12 and IL-23 in Inflammation 

      Chognard, Gaëlle; Bellemare, Lisa; Pelletier, Adam-Nicolas; Dominguez-Punaro, Maria C.; Beauchamp, Claudine; Guyon, Marie-Josée; Charron, Guy; Morin, Nicolas; Sivanesan, Durga; Kuchroo, Vijay; Xavier, Ramnik; Michnick, Stephen W.; Chemtob, Sylvain; Rioux, John D.; Lesage, Sylvie (Public Library of Science, 2014)
      IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet, little is known regarding the biology of these receptors. As the IL-12 and IL-23 receptors share a common subunit, it has been assumed that ...
    • Discovery and Functional Interpretation of Genetic Risk in Autoimmune Diseases 

      Hu, Xinli (2015-05-08)
      Autoimmune diseases are chronic and debilitating conditions arising from abnormal immune responses directed against normal body tissues; they collectively affect the lives of 5-10% of the world population. These diseases ...
    • Dynamic regulatory network controlling Th17 cell differentiation 

      Yosef, Nir; Shalek, Alex K.; Gaublomme, Jellert T.; Jin, Hulin; Lee, Youjin; Awasthi, Amit; Wu, Chuan; Karwacz, Katarzyna; Xiao, Sheng; Jorgolli, Marsela; Gennert, David; Satija, Rahul; Shakya, Arvind; Lu, Diana Y.; Trombetta, John J.; Pillai, Meenu R.; Ratcliffe, Peter J.; Coleman, Mathew L.; Bix, Mark; Tantin, Dean; Park, Hongkun; Kuchroo, Vijay K.; Regev, Aviv (2013)
      Despite their importance, the molecular circuits that control the differentiation of naïve T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term ...
    • Genetic and Epigenetic Fine-Mapping of Causal Autoimmune Disease Variants 

      Farh, Kyle Kai-How; Marson, Alexander; Zhu, Jiang; Kleinewietfeld, Markus; Housley, William J.; Beik, Samantha; Shoresh, Noam; Whitton, Holly; Ryan, Russell J.H.; Shishkin, Alexander A.; Hatan, Meital; Carrasco-Alfonso, Marlene J.; Mayer, Dita; Luckey, C. John; Patsopoulos, Nikolaos A.; De Jager, Philip L.; Kuchroo, Vijay K.; Epstein, Charles B; Daly, Mark J.; Hafler, David A.; Bernstein, Bradley E. (2014)
      Summary Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate ...
    • An IL-27/NFIL3 signaling axis drives Tim-3 and IL-10 expression and T cell dysfunction 

      Zhu, Chen; Sakuishi, Kaori; Xiao, Sheng; Sun, Zhiyi; Zaghouani, Sarah; Gu, Guangxiang; Wang, Chao; Tan, Dewar J.; Wu, Chuan; Rangachari, Manu; Pertel, Thomas; Jin, Hyun-Tak; Ahmed, Rafi; Anderson, Ana C.; Kuchroo, Vijay K. (2015)
      SUMMARY The inhibitory receptor Tim-3 has emerged as a critical regulator of the T cell dysfunction that develops in chronic viral infections and cancers. However, little is known regarding the signaling pathways that drive ...
    • Induction and molecular signature of pathogenic TH17 cells 

      Lee, Youjin; Awasthi, Amit; Yosef, Nir; Quintana, Francisco Javier; Xiao, Sheng; Peters, Anneli; Wu, Chuan; Kleinewietfeld, Markus; Kunder, Sharon R.; Hafler, David A.; Sobel, Raymond A.; Regev, Aviv; Kuchroo, Vijay Kumar (2012)
      Interleukin 17 (IL-17)-producing TH17 cells are often present at the sites of tissue inflammation in autoimmune diseases, which has lead to the conclusion that TH17 are main drivers of autoimmune tissue injury. However, ...
    • Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1 

      Wu, Chuan; Yosef, Nir; Thalhamer, Theresa; Zhu, Chen; Xiao, Sheng; Kishi, Yasuhiro; Regev, Aviv; Kuchroo, Vijay (2013)
      Th17 cells are highly proinflammatory cells critical for clearing extracellular pathogens and for induction of multiple autoimmune diseases1. IL-23 plays a critical role in stabilizing and reinforcing the Th17 phenotype ...
    • Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread 

      Czuczman, Mark A.; Fattouh, Ramzi; van Rijn, Jorik; Canadien, Veronica; Osborne, Suzanne; Muise, Aleixo M.; Kuchroo, Vijay K.; Higgins, Darren E.; Brumell, John H. (2014)
      Efferocytosis, the process by which dying/dead cells are removed by phagocytosis, plays an important role in development, tissue homeostasis and innate immunity1. Efferocytosis is mediated, in part, by receptors that bind ...
    • Loss of the Lupus Autoantigen Ro52/Trim21 Induces Tissue Inflammation and Systemic Autoimmunity by Disregulating the IL-23–Th17 Pathway 

      Espinosa, Alexander; Dardalhon, Valerie; Brauner, Susanna; Ambrosi, Aurelie; Higgs, Rowan; Sjöstrand, Maria; Eloranta, Maija-Leena; Ní Gabhann, Joan; Winqvist, Ola; Sundelin, Birgitta; Jefferies, Caroline A.; Rozell, Björn; Wahren-Herlenius, Marie; Quintana, Francisco Javier; Kuchroo, Vijay Kumar (The Rockefeller University Press, 2009)
      Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren's syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 ...
    • A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs 

      Fowler, Kevin D.; Kuchroo, Vijay Kumar; Chakraborty, Arup K. (Public Library of Science, 2012)
      The reason why IL-6 induces a pro-inflammatory response, while IL-10 induces an anti-inflammatory response, despite both cytokines activating the same transcription factor, STAT3, is not well understood. It is known that ...
    • Oct1 and OCA-B are selectively required for CD4 memory T cell function 

      Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N.; Snook, Jeremy; Kuchroo, Vijay K.; Yosef, Nir; Chan, Raymond C.; Regev, Aviv; Williams, Matthew A.; Tantin, Dean (The Rockefeller University Press, 2015)
      Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic ...
    • Pathogenic Potential ofCD4 T Cells in Autoimmune Diseases 

      Lee, Youjin (2015-05-22)
      The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 T helper ...
    • PD-L1 Regulates the Development, Maintenance, and Function of Induced Regulatory T Cells 

      Francisco, Loise Marie; Salinas, Victor H.; Brown, Keturah Elise; Vanguri, Vijay K.; Freeman, Gordon James; Kuchroo, Vijay Kumar; Sharpe, Arlene Helen (The Rockefeller University Press, 2009)
      Both the programmed death (PD) 1–PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg ...
    • Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90 

      Wang, Chenhui; Wu, Ling; Bulek, Katarzyna; Martin, Bradley N.; Zepp, Jarod A.; Kang, Zizhen; Liu, Caini; Herjan, Tomasz; Misra, Saurav; Carman, Julie A.; Gao, Ji; Dongre, Ashok; Han, Shujie; Bunting, Kevin D.; Ko, Jennifer S.; Xiao, Hui; Kuchroo, Vijay K.; Ouyang, Wenjun; Li, Xiaoxia (2012)
      Act1 is an essential adaptor molecule in IL-17-mediated signaling and is recruited to the IL-17 receptor upon IL-17 stimulation. Here, we report that Act1 is a client protein of the molecular chaperone, Hsp90. The Act1 ...
    • Ptpn22 and Cd2 Variations Are Associated with Altered Protein Expression and Susceptibility to Type 1 Diabetes in Nonobese Diabetic Mice 

      Fraser, Heather I.; Howlett, Sarah; Clark, Jan; Rainbow, Daniel B.; Stanford, Stephanie M.; Wu, Dennis J.; Hsieh, Yi-Wen; Maine, Christian J.; Christensen, Mikkel; Kuchroo, Vijay; Sherman, Linda A.; Podolin, Patricia L.; Todd, John A.; Steward, Charles A.; Peterson, Laurence B.; Bottini, Nunzio; Wicker, Linda S. (AAI, 2015)
      By congenic strain mapping using autoimmune NOD.C57BL/6J congenic mice, we demonstrated previously that the type 1 diabetes (T1D) protection associated with the insulin-dependent diabetes (Idd)10 locus on chromosome 3, ...
    • The Role of Nutrient Sensing in Macrophage Polarization 

      Covarrubias, Anthony Joseph (2016-01-26)
      Macrophages are essential immune cells that belong to the innate immune system and are key orchestrators in the initiation and resolution stages of inflammation. Macrophages are found in every organ throughout the body ...
    • Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation 

      Talbot, Sebastien; Abdulnour, Raja-Elie E; Burkett, Patrick Ryland; Lee, Seungkyu; Cronin, Shane J.F.; Pascal, Maud A.; Laedermann, Cedric; Foster, Simmie Lorene; Tran, Johnathan V.; Lai, Nicole Yin Yee; Chiu, Isaac Ming-Cheng; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David P; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M.; Kuchroo, Vijay Kumar; Bean, Bruce Palmer; Levy, Bruce David; Woolf, Clifford (Elsevier BV, 2015)
      Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release ...
    • T cell–derived inducible nitric oxide synthase switches off TH17 cell differentiation 

      Yang, Jianjun; Zhang, Ruihua; Lu, Geming; Shen, Yu; Peng, Liang; Zhu, Chen; Cui, Miao; Wang, Weidong; Arnaboldi, Paul; Tang, Meng; Gupta, Monica; Qi, Chen-Feng; Jayaraman, Padmini; Zhu, Hongfa; Jiang, Bo; Chen, Shu-hsia; He, John Cijiang; Ting, Adrian T.; Zhou, Ming-Ming; Kuchroo, Vijay K.; Morse, Herbert C.; Ozato, Keiko; Sikora, Andrew G.; Xiong, Huabao (The Rockefeller University Press, 2013)
      RORγt is necessary for the generation of TH17 cells but the molecular mechanisms for the regulation of TH17 cells are still not fully understood. We show that activation of CD4+ T cells results in the expression of inducible ...