Robert Tigelaar, M.D.

Professor of Dermatology and Immunobiology

Research Interests

Dr. Robert Tigelaar’s research focuses on dendritic epidermal T cells (DETC), cells which populate the skin of all normal strains of mice and express homogeneous VGamma5/Vdelta1 TCRs lacking junctional (CDR3 region) diversity. Use of different strains of TCRdelta-/- mice and selective reconstitution of such mice via adoptive transfer has recently shown that VGamma5+ DETC, but not other gamma delta cells, down-regulate a variety of cutaneous inflammatory responses, including a spontaneous, localized, genetically-dependent, TCR alpha beta+ T cell-dependent, and environmentally-dependent, chronic dermatitis that shares several features of human atopic dermatitis. Current collaborative studies with Dr. Adrian Hayday (Guy’s Hospital, London) include: 1) Characterizing the genes expressed by “resting” and “activated” DETC by serial analysis of gene expression (SAGE) and comparing such expression patterns with other IEL and recirculating T cell subsets. 2) Investigating selected candidate DETC anti-inflammatory cytokines/effector molecules by reconstituting TCR delta-/- recipients with DETC precursors rendered deficient (via gene “knockout” or siRNA “knock-down") in candidate anti-inflammatory molecules. 3) Utilizing genome-wide microsatellite mapping, to identify the genetic interval(s), and ultimately the specific genes, controlling susceptibility/ resistance to the spontaneous dermatitis that develops in some, but not other TCR delta -/- mice; and 4) Utilizing cellular, molecular and genetic studies to identify the physiologic ligands for TCR gamma/delta+ T cells that trigger both their positive selection in the thymus and their activation in peripheral epithelial tissues such as the skin and GI tract.

Education:	1964, B.A., Hope College 1968, M.D., University of Michigan Residency: University of Washington
Training:	Fellowship: NIH

Selected Publications

• Hayday A, Tigelaar R. Regulatory Lymphocytes: Immunoregulation in the tissues by γδ T cells. Nat Rev Immunol. 3(3):233-42, 2003.
• Girardi M, Glusac E, Lewis J, Filler R, Hayday AC, Tigelaar RE. Resident skin-specific γδ T cells provide local, nonredundant regulation of cutaneous inflammation., J Exp Med, 195: 855-867, 2002
• Hara H. Kishihara K. Matsuzaki G. Takimoto H. Tsukiyama T. Tigelaar RE. Nomoto K. Development of dendritic epidermal T cells with a skewed diversity of γδ TCRs in Vδ;1-deficient mice. Journal of Immunology. 165(7):3695-705, 2000
• Leachman SA, Tigelaar RE, Shylankevich M, Slade MD, Irwin M, Chang E, Wu TC, XIAO W, Pazhani S, Zelterman D, Brandsma J. GM-CSF priming plus papillomavirus E6 DNA vaccination: Effects on papilloma formation and regression in the CRPV-rabbit model. J Virology. 74(18):8700-8, 2000
• Herrick CA, MacLeod H, Glusac E, Tigelaar RE, Bottomly K. Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J Clin Invest, March 2000, Volume 105, Number 6, 765-775.
• Laky K, Lefrancois L, Lingenheld EG, Ishikawa H, Lewis JM, Olson S, Suzuki K, Tigelaar RE, Puddington L. Enterocyte Expression of IL-7 Induces Development of γδ T Cells and Peyer's Patches. J Exp Med, 191(9): 1569-80, 2000.
• Girardi M, Oppenheim D, Lewis J, Filler R, Tigelaar RE, Hayday AC. The regulation of squamous cell carcinoma development by γδ T cells, Science. 294:605-609, 2001.
• Berger C. Xu A. Hanlon D. Lee C. Schechner J. Glusac E. Christensen I. Snyder E. Holloway V. Tigelaar R. Edelson R. Induction of human tumor-loaded dendritic cells. Int J Cancer. 91:438-447, 2001
• Girardi M, Glusac E, Lewis J, Filler R, Hayday AC, Tigelaar RE. Resident skin-specific γδ T cells provide local, non-redundant regulation of cutaneous inflammation. J Exp Med, 195: 855-867, 2002.
• Girardi M, Oppenheim DE, Glusac EJ, Filler R, Balmain A, Tigelaar R and Hayday AC. Characterizing the protective component of the γδ T cell response to transplantable squamous cell carcinoma. J Invest Dermatol, In press, 2003.
• Ramsburg E, Tigelaar R, Craft J and Hayday A. Age-dependent requirements for γδ T cells in the primary but not secondary protective immune response against an intestinal parasite. J Exp Med 198(9):1-13, 2003.
• Pennington DJ, Silva-Santos B, Shires J, Theodoridis E, Pollitt C, Wise EL, Tigelaar RE, Owen MJ, Hayday AC. The inter-relatedness and interdependence of mouse T cell receptor γδ (+) and "$ (+) cells. Nat Immunol. 4(10):991-8, 2003.
• Girardi M, Glusac E, Filler RB, Roberts SJ, Propperova I, Lewis J, Tigelaar RE, Hayday AC. The Distinct Contributions of Murine T Cell Receptor TCRγδ+ and TCR "$+ T Cells to Different Stages of Chemically Induced Skin Cancer. J Exp Med 1;198(5):747-755, 2003.
• Hayday A, Tigelaar R. Regulatory Lymphocytes: Immunoregulation in the tissues by γδ T cells.Nat Rev Immunol. 3(3):233-42, 2003.
• Laky K, Lewis JM, Tigelaar RE, Puddington L. Distinct requirements for IL-7 in development of TCR γδ cells during fetal and adult life. J Immunol. 170(8):4087-94, 2003.
• Herrick C, Lan X, McKenzie A, Tigelaar R, Bottomly K. IL-13 is necessary, not simply sufficient for epicutaneously induced Th2 responses to soluble protein antigen. J Immunology, 170:2488-95, 2003
• Girardi M, Sherling MA, Filler, RB, Shires J, Theodoridis E, Hayday AC, Tigelaar RE. Anti-inflammatory effects in the skin of thymosin-4 splice variants. Immunology, 109:1-7, 2003.
• Laky K, Lewis JM, Tigelaar RE, Puddington L. Distinct Requirements for IL-7 in Development of TCRγδ Cells During Fetal and Adult Life. J Immunol. 70:4087-94, 2003.
• Girardi M, Oppenheim DE, Glusac EJ, Filler R, Balmain A, Tigelaar R and Hayday AC. Characterizing the protective component of the γδ T cell response to transplantable squamous cell carcinoma. J Invest Dermatol, 122:699-706, 2004
• Roark CL, Aydintug MK, Lewis J, Yin X, Lahn M, Hahn YS, Born WK, Tigelaar RE, O'Brien RL. Subset-specific, uniform activation among Vg6/Vd1+ γδ T cells elicited by inflammation. J Leukoc Biol. 75(1):68-75, 2004.
• Lewis JM, Girardi M, Roberts SJ, Barbee S, Hayday AC, Tigelaar RE. The physiologic cutaneous intraepithelial gamma delta T cell repertoire is established by a thymic stromal determinant. Nat Immunol. 7(8): 843-850, 2006.
• Girardi M, Lewis JM, Filler RB, Hayday AC, Tigelaar RE. Environmentally responsive and reversible regulation of epidermal barrier function by gamma delta T cells. J Invest Dermatol. 126:808-14, 2006.
• Oppenheim DE, Roberts SJ, Clarke SL, Filler R, Lewis JM, Tigelaar RE, Girardi M, Hayday AC. Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance. Nat Immunol. 6(9):928-37, 2005.
• Pennington DJ, Vermijlen D, Wise EL, Clarke SL, Tigelaar RE, Hayday AC. The integration of conventional and unconventional T cells that characterizes cell-mediated responses. Adv Immunol. 87:27-59, 2005.

Contact

Academic Office
Yale Dermatopathology Laboratory
15 York Street, LMP 5031
New Haven, CT 06520-8059

Phone
(203) 785-4968

Email
robert.tigelaar@yale.edu