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Dr. Mucida studies how the immune system associated with intestinal mucosae is able to generate efficient immune responses without jeopardizing its tolerance to innocuous antigens, and what happens when this balance is disrupted.
The human intestinal mucosae, which have a surface area of about 300 square meters, form the body’s largest surface that is exposed to exogenous antigens. The intestines absorb approximately 100 grams of dietary proteins each day and are also home to an estimated 100 trillion commensal bacteria, about 10 times the number of cells of the human body. To mediate immunity over such a large and active area, there are more lymphocytes associated with the intestine than there are in the entire rest of the human body.
Most intestinal lymphocytes display an activated phenotype, yet under normal physiological conditions they remain in an immune quiescent state. This so-called “gut physiological inflammation” is maintained by distinct regulatory mechanisms, including regulatory lymphocytes and dendritic cells. The Mucida laboratory works on understanding how the immune system is regulated in intestinal mucosa and how it maintains a balance between efficient immune response and tolerance to innocuous antigens.
One of the goals of his laboratory is to characterize the cellular and molecular mechanisms that lead to the development of pro-inflammatory and regulatory cells at the mucosal surfaces, both from the innate and the adaptive immune system. Dr. Mucida has shown that the intestine is able to efficiently induce regulatory lymphocytes that can prevent allergy and other inflammatory processes and that diet provides precursors that can be used for the maintenance of intestinal homeostasis. He has found that a vitamin A metabolite, retinoic acid, produced by intestinal dendritic cells, is able to modulate the development of inflammatory and regulatory cells.
A second interest of Dr. Mucida’s lab is to understand how exposure to different classes of commensal bacteria affects the development and differentiation of immune cells and susceptibility to inflammatory processes. The crucial role of the microbiota for the development and maturation of the immune system is demonstrated by studies on germ-free animals, which bear an immature immune system. However, not only the number but also the type of bacteria can differentially influence immune responses, with some classes of bacteria inhibiting while other classes induce inflammatory cells. Dr. Mucida has found that commensal bacteria are a crucial factor involved in the modulation of inflammatory cells in the intestine. Although CD4 helper T cells are crucial for the generation of efficient immune responses, uncontrolled CD4 helper T cells can pose a threat to an organism, particularly in chronically stimulated sites such as the mucosal surfaces. In conventionally raised mice, but not in germ-free mice, the intestinal environment efficiently suppresses CD4 helper T cell inflammatory activity and redirects CD4 T cells to become CD8-like cytotoxic T cells.
The Mucida laboratory also uses several animal models to study intestinal and systemic infections to dissect the molecular and cellular pathways triggered by infectious agents and how they can be modulated to achieve protective, but not destructive, immune responses. Although the great majority of antigenic sources in the mucosal surfaces are nondeleterious, the intestine is also a major site of entry for viruses, pathogenic bacteria, fungi and parasites. The requirement for a rapid and efficient immune protection, however, contrasts with the possibility of unregulated or excessive immune responses toward gut antigens, which can lead to allergies and severe inflammatory bowel diseases.
Dr. Mucida received his undergraduate degree in biology, with an emphasis on biochemistry and immunology, from the Federal University of Minas Gerais in Brazil in 2000. He received his Ph.D. jointly from the University of São Paulo and New York University in 2005. After postdoctoral studies at the La Jolla Institute for Allergy and Immunology from 2006 to 2010, he joined The Rockefeller University as assistant professor in 2010.
Dr. Mucida has received 2007 and 2008 fellowship awards from the Diabetes and Immune Disease National Research Institute, 2009 and 2012 career development awards from the Crohn’s and Colitis Foundation of America, a 2011 New Scholar Award on Aging from the Ellison Foundation and the 2012 Research Award from the Irma T. Hirschl/Monique Weill-Caulier Trusts.
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