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Hideki Ueno, MD, PhD

 

 

Investigator

Director, Immunomonitoring Core

 

3434 Live Oak, Dallas, TX, 75204

214-820-9917

hidekiu@baylorhealth.edu

 

Education

MD, Kyoto University, Kyoto, Japan

PhD, Graduate School of Medicine, Kyoto University, Kyoto, Japan

 

The current major focus of my lab is on human CD4+ T cell subsets, in particular T follicular helper (TFH) cells. TFH cells represent a major CD4+ T cell subset specialized for the provision of help for antibody responses. TFH response needs to be regulated, as both insufficient and increased responses cause health problems: Insufficient TFH response causes failure in the development of antibody responses, for example in response to vaccination. Increased TFH response causes autoimmunity by promoting the generation of autoantibodies. Therefore, understanding the biology of human TFH cells is essential to define the mechanisms responsible for impaired antibody response in infection and vaccination, and to understand the pathogenesis of autoantibody-mediated autoimmune diseases. We have shown that human TFH cells found in human blood are composed of functionally distinct subsets, and an alteration in the balance of blood TFH subsets is associated with the pathogenesis of human autoimmune diseases. Furthermore, our recent study shows that the developmental mechanism of TFH cells is distinct between humans and mice. The three cytokines, IL-12, IL-23, and TGF-b, play dominant roles for the generation of human TFH cells.

 

Major Contribution to Science (bullet points & key refs)

1. Phenotypic and functional characterization of human dendritic cell subsets

  • Ueno H, Tcherepanova I, Reygrobellet O, Laughner E, Ventura C, Palucka AK, Banchereau J. Dendritic cell subsets generated from CD34+ hematopoietic progenitors can be transfected with mRNA and induce antigen-specific cytotoxic T cell responses. J. Immunol Methods. 2004;285(2):171-80.
  • Cao T*, Ueno H*, Glaser C, Fay JW, Palucka AK, Banchereau J. Both Langerhans cells and interstitial DC cross-present melanoma antigens and efficiently activate antigen-specific CTL. Eur J Immunol. 2007;37(9):2657-67.
  • Klechevsky E, Morita R, Liu M, Cao Y, Coquery S, Thompson-Snipes L, Briere F, Chaussabel D, Zurawski G, Palucka AK, Reiter Y, Banchereau J, Ueno H. Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells. Immunity. 2008;29(3):497-510. PMCID: PMC2688399.

 

 

2. Development of a novel approach to determine human antigen-specific T cell repertoires

  • Palucka AK*, Ueno H*, Connolly J, Kerneis-Norvell F, Blanck JP, Johnston DA, Fay J*, Banchereau J*. Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. J Immunother. 2006;29(5):545-57.
  • Vence L, Palucka AK, Fay JW, Ito T, Liu YJ, Banchereau J, Ueno H. Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2007;104(52):20884-9.
  • Chujo D, Foucat E, Takita M, Itoh T, Sugimoto K, Shimoda M, Yagi K, Yamagishi K, Tamura Y, Yu L, Naziruddin B, Levy MF, Ueno H*, Matsumoto S*. Emergence of a Broad Repertoire of GAD65-specific T Cells in Type 1 Diabetes Patients with Graft Dysfunction after Allogeneic Islet Transplantation. Cell Transplant. 2012;21(12):2783-95.
  • Chujo D, Foucat E, Nguyen TS, Chaussabel D, Banchereau J, Ueno H. ZnT8-Specific CD4(+) T Cells Display Distinct Cytokine Expression Profiles between Type 1 Diabetes Patients and Healthy Adults. PloS one. 2013;8(2):e55595. PMCID: 3563599.

 

3. Identification of developmental pathways and functionally distinct subsets in human T follicular helper (TFH) cells

  • Schmitt N, Morita R, Bourdery L, Bentebibel SE, Zurawski SM, Banchereau J, Ueno H. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity. 2009;31(1):158-69.
  • Dullaers M, Li D, Xue Y, Ni L, Gayet I, Morita R, Ueno H, Palucka KA, Banchereau J, Oh S. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. Immunity. 2009;30(1):120-9.
  • Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108-21.
  • Bentebibel S-E, Schmitt N, Banchereau J, Ueno H. Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers. Proc Natl Acad Sci U S A. 2011;10.1073/pnas.1100898108.
  • Bentebibel SE, Lopez S, Obermoser G, Schmitt N, Mueller C, Harrod C, Flano E, Mejias A, Albrecht RA, Blankenship D, Xu H, Pascual V, Banchereau J, Garcia-Sastre A, Palucka AK, Ramilo O, Ueno H. Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Science Translational Medicine. 2013;5(176):176ra32. PMCID: 3621097.
  • Schmitt N, Bustamante J, Bourdery L, Bentebibel SE, Boisson-Dupuis S, Hamlin F, Tran MV, Blankenship D, Pascual V, Savino DA, Banchereau J, Casanova JL, Ueno H. IL-12 receptor beta1 deficiency alters in vivo T follicular helper cell response in humans. Blood. 2013;121(17):3375-85. PMCID: 3637013.
  • Schmitt N, Liu Y, Bentebibel S, Munagala I, Bourdery L, Venuprasad K, Banchereau J, Ueno H. TGF-b Co-opts STAT3/STAT4 Signaling to Promote Human T Follicular Helper Cell Differentiation. Nat Immunol. 2014; In press. doi:10.1038/ni.2947.

 

4. Major Review Articles

  • Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, Di Pucchio T, Connolly J, Fay JW, Pascual V, Palucka AK, Banchereau J. Dendritic cell subsets in health and disease. Immunol Rev. 2007;219:118-42.
  • Ueno H, Palucka AK, Banchereau J. The expanding family of dendritic cell subsets. Nat Biotechnol. 2010;28(8):813-5.
  • Ueno H, Schmitt N, Klechevsky E, Pedroza-Gonzalez A, Matsui T, Zurawski G, Oh S, Fay J, Pascual V, Banchereau J, Palucka K. Harnessing human dendritic cell subsets for medicine. Immunol Rev. 2010;234(1):199-212. PMCID: PMC2847489.
  • Ueno H, Schmitt N, Palucka AK, Banchereau J. Dendritic cells and humoral immunity in humans. Immunol Cell Biol. 2010;88(4):376-80. PMCID: PMC2865578.
  • Banchereau J, Klechevsky E, Schmitt N, Morita R, Palucka K, Ueno H. Harnessing human dendritic cell subsets to design novel vaccines. Annals of the New York Academy of Sciences. 2009;1174:24-32. PMCID: PMC2759267.
  • Chaussabel D, Ueno H, Banchereau J, Quinn C. Data management: it starts at the bench. Nat Immunol. 2009;10(12):1225-7. PMCID: PMC2788787.
  • Ueno H, Klechevsky E, Schmitt N, Ni L, Flamar AL, Zurawski S, Zurawski G, Palucka K, Banchereau J, Oh S. Targeting human dendritic cell subsets for improved vaccines. Seminars Immunol. 2011.
  • Schmitt N, Ueno H. Blood Tfh cells come with colors. Immunity. 2013;39(4):629-30.
  • Schmitt N, Bentebibel SE, Ueno H. Phenotype and functions of memory Tfh cells in human blood. Trends Immunol. 2014.
  • Ueno H, Banchereau J, Vinuesa CG. Pathophysiology of T follicular helper cells. Nat Immunol. 2014 In press.

 

 

Current grants

Novel innate and Adaptive Immunity Pathways Lead to Human systemic Autoimmunity (Autoimmunity Center of Excellence)

NIH, U19 082715

06/01/14 – 05/31/19

(Project 3, Principal Investigator: Altered T follicular helper responses in human autoimmune diseases)                                                                                                                                              

 

Systems Analysis Vaccine Responses in healthy & Hyporesponsive Humans

NIH, U19 AI089987

06/01/10 – 05/31/15

(Project 2, Principal Investigator: Vaccine Induced Activation of T Follicular Helper Cell Subsets)

 

Altered T follicular helper cell subsets in active pediatric SLE

Alliance for Lupus Research, 220006

02/01/12 – 02/01/15

Principal Investigator

 

 

Publications (out of 61 total from 1994 to 2014)

Key publications during the past 5 years (2009 to 2014)

 

1. Schmitt N, Liu Y, Bentebibel S, Munagala I, Bourdery L, Venuprasad K, Banchereau J, Ueno H. TGF-b co-opts signaling via STAT3/STAT4 to promote the differentiation of human TFH cells Nature Immunol. 2014;doi:10.1038/ni.2947.

2. Schmitt N, Bentebibel SE, Ueno H. Phenotype and functions of memory Tfh cells in human blood. Trends Immunol. 2014;10.1016/j.it.2014.06.002.

3. Schmitt N, Ueno H. Blood Tfh cells come with colors. Immunity. 2013;39(4):629-30.

4. Schmitt N, Bustamante J, Bourdery L, Bentebibel SE, Boisson-Dupuis S, Hamlin F, Tran MV, Blankenship D, Pascual V, Savino DA, Banchereau J, Casanova JL, Ueno H. IL-12 receptor beta1 deficiency alters in vivo T follicular helper cell response in humans. Blood. 2013;121(17):3375-85. PMCID: 3637013.

5. Obermoser G, Presnell S, Domico K, Xu H, Wang Y, Anguiano E, Thompson-Snipes L, Ranganathan R, Zeitner B, Bjork A, Anderson D, Speake C, Ruchaud E, Skinner J, Alsina L, Sharma M, Dutartre H, Cepika A, Israelsson E, Nguyen P, Nguyen QA, Harrod AC, Zurawski SM, Pascual V, Ueno H, Nepom GT, Quinn C, Blankenship D, Palucka K, Banchereau J, Chaussabel D. Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines. Immunity. 2013;38(4):831-44. PMCID: 3681204.

6. Chujo D, Foucat E, Nguyen TS, Chaussabel D, Banchereau J, Ueno H. ZnT8-Specific CD4(+) T Cells Display Distinct Cytokine Expression Profiles between Type 1 Diabetes Patients and Healthy Adults. PloS one. 2013;8(2):e55595. PMCID: 3563599.

7. Bentebibel SE, Lopez S, Obermoser G, Schmitt N, Mueller C, Harrod C, Flano E, Mejias A, Albrecht RA, Blankenship D, Xu H, Pascual V, Banchereau J, Garcia-Sastre A, Palucka AK, Ramilo O, Ueno H. Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Science Translational Medicine. 2013;5(176):176ra32. PMCID: 3621097.

8. Chujo D, Foucat E, Takita M, Itoh T, Sugimoto K, Shimoda M, Yagi K, Yamagishi M, Tamura Y, Yu L, Naziruddin B, Levy MF, Ueno H, Matsumoto S. Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation. Cell transplantation. 2012;21(12):2783-95.

9. Ueno H, Klechevsky E, Schmitt N, Ni L, Flamar AL, Zurawski S, Zurawski G, Palucka K, Banchereau J, Oh S. Targeting human dendritic cell subsets for improved vaccines. Seminars in immunology. 2011;23(1):21-7. PMCID: 3071344.

10. Palucka K, Ueno H, Banchereau J. Recent developments in cancer vaccines. J Immunol. 2011;186(3):1325-31.

11. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain

specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108-21.

12. Bentebibel SE, Schmitt N, Banchereau J, Ueno H. Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers. Proceedings of the National Academy of Sciences. 2011;108(33):E488-97. PMCID: 3158181.

13. Ueno H, Schmitt N, Palucka AK, Banchereau J. Dendritic cells and humoral immunity in humans. Immunology and cell biology. 2010;88(4):376-80. PMCID: PMC2865578.

14. Ueno H, Schmitt N, Klechevsky E, Pedroza-Gonzalez A, Matsui T, Zurawski G, Oh S, Fay J, Pascual V, Banchereau J, Palucka K. Harnessing human dendritic cell subsets for medicine. Immunological reviews. 2010;234(1):199-212. PMCID: PMC2847489.

15. Ueno H, Palucka AK, Banchereau J. The expanding family of dendritic cell subsets. Nat Biotechnol. 2010;28(8):813-5.

16. Palucka K, Ueno H, Zurawski G, Fay J, Banchereau J. Building on dendritic cell subsets to improve cancer vaccines. Current opinion in immunology. 2010;22(2):258-63. PMCID: PMC2854185.

17. Schmitt N, Morita R, Bourdery L, Bentebibel SE, Zurawski SM, Banchereau J, Ueno H. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helperlike cells through interleukin-12. Immunity. 2009;31(1):158-69. PMCID: PMC2731623.

 

 



Baylor Health Care System is located in Dallas, Texas