Warren Strober, M.D.
Senior Investigator
Chief, Mucosal Immunity Section
Mucosal Immunity Section
Dr. Strober is a leader in the study of mucosal antibody responses, oral tolerance, and gastroenterological diseases caused by immunologic abnormalities. His discoveries concerning the mucosal immune system have formed the basis of our knowledge of IgA B cell development and the mechanisms of mucosal inflammation.
Dr. Strober is the recipient of numerous awards, including the Distinguished Achievement Award of the American Gastroenterological Association and the PHS Distinguished Achievement Medal. In addition, he has been awarded an Honorary Doctorate from the Humboldt University, Berlin. Dr Strober has provided leadership to the scientific community as chair of the American Board of Allergy and Immunology and as president of the Society for Mucosal Immunity.
Other permanent members of the Mucosal Immunity Section include Dr. Ivan Fuss and Dr. Atsushi Kitani. Dr. Fuss is a staff clinician in the section and has a distinguished research record in the study of murine models of inflammation; in addition, Dr. Fuss has been a leader in the conduct of clinical trials of new agents for the treatment of inflammatory bowel disease. Dr. Kitani is a staff scientist in the section and has played a prominent role in the conduct of studies focusing on the molecular mechanisms underlying mucosal inflammation. He has vast experience in the use of molecular constructs both as research tools and as therapeutic modalities.
Description of Research Program
The Mucosal Immunity Section (MIS) conducts a broad spectrum of studies on the immune system of mucosal surfaces. Over the years, the section has gained prominence for studies of basic mechanisms of the mucosal immune response and diseases resulting from disorders of these mechanisms.
In one major area of study, section scientists have made extensive use of experimental models to understand the complex cellular and molecular events governing mucosal inflammation. On the one hand this has led to new insights into the effector and regulatory mechanisms at play during gastrointestinal inflammation and, on the other hand, to the development of new approaches to the treatment of human counterpart diseases: Crohn’s disease and ulcerative colitis. In one such approach, the treatment of Th1/Th17-based mucosal inflammation with anti-IL-12p40 has shown promise as a treatment of Crohn’s disease in a human clinical trial conducted by members of the section. In another such approach, the treatment of NKT cell/IL-13 –based mucosal inflammation with anti-IL-13 agents has resulted in clinical studies of therapies for ulcerative colitis using agents that neutralize IL-13.
In related studies focusing on the molecular basis of mucosal inflammation, section scientists have conducted ground-breaking studies of the mechanism by which CARD15 (NOD2) polymorphisms cause Crohn’s disease. They have shown that NOD2 normally down-regulates innate immune responses via TLR signaling and that CARD15 polymorphisms in Crohn’s disease compromise this regulation and thus lead to excessive production of Th1/Th17 cytokine production.
In other basic studies of the mechanisms of mucosal inflammation, section scientists have elucidated the effector mechanisms underlying regulatory T cell activity and have conducted extensive studies of the molecular regulation of cytokine synthesis.
Finally, scientists in the section couple their interests in diseases related to mucosal immunity with interests in immunodeficiency diseases. This is evident in long-standing studies of common variable immunodeficiency, IgA deficiency, and other immunodeficiency states.
The MIS has long been a breeding ground for highly regarded immunologists, and this teaching tradition is alive and well in the section. Fellows are given well-defined and independent projects and are encouraged to be creative within their assigned areas (or outside of their assigned areas, at times).
Selected Publications
(View list in PubMed.)
Watanabe T, Kitani A, Murray PJ, Strober W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol. 2004. 5(8): 800-808.
Strober W, Fuss I, Boirivant M, Kitani A. Insights into the mechanism of oral tolerance derived from the study of models of mucosal inflammation. Ann N Y Acad Sci. 2004. 1029: 115-131.
Mannon PJ, Fuss IJ, Mayer L, Elson CO, Sandborn WJ, Present D, Dolin B, Goodman N, Groden C, Hornung RL, Quezado M, Neurath MF, Salfeld J, Veldman GM, Schwertschlag U, Strober W, Anti-IL-12 Crohn's Disease Study Group. Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med. 2004. 351(20): 2069-2079.
Fuss IJ, Heller F, Boirivant M, Leon F, Yoshida M, Fichtner-Feigl S, Yang Z, Exley M, Kitani A, Blumberg RS, Mannon P, Strober W. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004. 113(10): 1490-1497.
Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H, Strober W. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol. 2004. 172(2): 834-842.
Kitani A, Fuss I, Nakamura K, Kumaki F, Usui T, Strober W. Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med. 2003. 198(8): 1179-1188.
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