Biosketch / Results /
Dan LittmanHelen L. and Martin S. Kimmel Professor of Molecular Immunology, Department of Pathology;Professor, Department of Microbiology
Education1980 — Washington University, St. Louis, Missouri, Graduate Education
Research SummaryOur laboratory investigates 1) the molecular events underlying T-lymphocyte differentiation and activation and 2) how the human immunodeficiency virus (HIV) enters target cells and causes systemic depletion of helper T cells. In both areas, we study the functions of T-cell surface molecules and their interactions with intracellular signal transducing components.
During development, CD4 and CD8 glycoproteins are co-expressed on immature thymocytes (double-positive cells), which are then selected according to their ability to interact productively with host major histocompatibility complex (MHC) molecules expressed on thymic epithelium. Cells with T-cell receptors specific for MHC class I shut off CD4 and commit to becoming cytotoxic cells, while cells with T-cell receptors for MHC class II shut off CD8 and become helper cells. We use gene targeting and transgenic technology in mice to study how the double-positive cells commit to either of the two major T-lymphocyte lineages.
In our studies with immunodeficiency viruses, we seek to understand how the interaction of viral envelope glycoproteins with CD4 and various chemokine receptors on the target cells results in membrane fusion and viral entry. We are also developing mouse model systems to determine how HIV infection causes loss of CD4+ helper T cells. In related studies, the functions of chemokine receptors in development and in inflammatory responses are being investigated.
Research InterestsT-lymphocyte Development and Retroviral Pathogenesis
Identification of Natural RORgamma Ligands that Regulate the Development of Lymphoid Cells
Santori, Fabio R; Huang, Pengxiang; van de Pavert, Serge A; Douglass, Eugene F Jr; Leaver, David J; Haubrich, Brad A; Keber, Rok; Lorbek, Gregor; Konijn, Tanja; Rosales, Brittany N; Rozman, Damjana; Horvat, Simon; Rahier, Alain; Mebius, Reina E; Rastinejad, Fraydoon; Nes, W David; Littman, Dan R
2015-02-08; 1550-4131,Cell metabolism - id: 1456642, year: 2015 Journal Article
Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease
Scher, Jose U; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G; Littman, Dan R; Abramson, Steven B
2015-02-06; 2326-5205,Arthritis & rheumatology - id: 1453542, year: 2015 Journal Article
The microbiota conditions CX3CR1+ intestinal mononuclear phagocytes to limit intestinal inflammation
Diehl, G; Galan, C; Longman, R; Egawa, T; Yang, Y; Littman, D
2014-07-02; 0022-1767,Journal of immunology (1950) - id: 1058322, year: 2014
GPR15 mediated homing controls immune homeostasis in the large intestine mucosa
Kim, S; Xiang, W; Kwak, C; Yang, Y; Lin, X; Ota, M; Sarpel, U; Rifkin, D; Xu, R; Littman, D
2014-07-02; 0022-1767,Journal of immunology (1950) - id: 1058262, year: 2014
CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22
Longman, Randy S; Diehl, Gretchen E; Victorio, Daniel A; Huh, Jun R; Galan, Carolina; Miraldi, Emily R; Swaminath, Arun; Bonneau, Richard; Scherl, Ellen J; Littman, Dan R
2014-07-25; 0022-1007,Journal of experimental medicine - id: 1075092, year: 2014 JOURNAL ARTICLE