Heads of Laboratories
Laboratory of Mucosal Immunology
At the surface of the intestinal lining, immune responses must be carefully balanced: Invasive pathogens must be eliminated or excluded, while nutrients and trillions of commensal microbes that contribute to homeostasis must be tolerated. Dr. Mucida studies how the immune system associated with intestinal mucosae walks this fine line by generating efficient protective responses without jeopardizing its tolerance to innocuous antigens.
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. To mediate immunity over such a large and active area, there are more lymphocytes associated with the intestine than 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 these regulatory mechanisms and how they maintain a balance between responsiveness and tolerance.
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 using metabolites derived from diet. 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. His laboratory uses imaging and genetic tools to investigate innate and adaptive immune cell dynamics in the intestinal tissue, and how they assimilate different environmental cues to maintain the integrity of the epithelial barrier and intestinal homeostasis.
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. 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, his laboratory has found that the intestinal environment efficiently suppresses T cell inflammatory activity and redirects T cells toward protective, yet non-pathogenic T cell lineages.
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 rapid and efficient immune protection, however, allows the possibility of unregulated or excessive immune responses toward gut antigens, which can lead to allergies and severe inflammatory bowel diseases.
B.S. in biochemistry and immunology, 2000
Federal University of Minas Gerais
University of São Paulo and New York University
University of São Paulo, 2005–2006
La Jolla Institute for Allergy and Immunology, 2006–2010
Assistant Professor, 2010–2016
Associate Professor, 2016–
The Rockefeller University
New Scholar Award on Aging, Ellison Foundation, 2011
Crohn’s and Colitis Foundation of America Career Development Award, 2012
Irma T. Hirschl/Monique Weill-Caulier Trust Research Award, 2012
Kenneth Rainin Foundation Innovator Award, 2014
Reis, B.S. et al. Leptin receptor signaling in T cells is required for Th17 differentiation. J. Immunol. 194, 5253–5260 (2015).
Rogoz, A. et al. A 3-D enteroid-based model to study T-cell and epithelial cell interaction. J. Immunol. Methods 421, 89–95 (2015).
Reis, B.S. et al. Transcription factor T-bet regulates intra-epithelial lymphocyte functional maturation. Immunity 41, 244–256 (2014).
Reis, B.S. et al. Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4+ T cell immunity. Nat. Immunol. 14, 271–280 (2013).
Mucida, D. et al. Transcriptional reprogramming of mature CD4+ helper T cells generates distinct MHC class II–restricted cytotoxic T lymphocytes. Nat. Immunol. 14, 281–289 (2013).