Rodney Newberry, M.D.

Professor
Internal Medicine
Gastroenterology

Immunology Program

  • 314 362-2671

  • 314 362-2670

  • 314 362-2609

  • 8124

  • 10th floor CSRB-NT room 1027

  • rnewberry@wustl.edu

  • http://newberrylab.im.wustl.edu/

  • Immunology, Gastrointestinal Tract, Inflammatory Bowel Disease

  • Mucosal Immunology

Research Abstract:

The intestinal immune system is continuously exposed to antigens ranging from innocuous food substances to potential pathogens. In this challenging environment the intestinal immune system must both protect the host from infection and mitigate potential damage from over exuberant immune responses to innocuous antigens. Studies in our lab revolve around two themes investigating how the intestinal immune system accomplishes this delicate balancing act.

The first body of work investigates how intestinal dendritic cells appropriately guide immune responses to the wide array of antigens encountered in the intestine. We have identified a novel function for goblet cells delivering luminal antigens to intestinal dendritic cells. This antigen deliver pathway selectively targets CD103+ dendritic cells that have unique capacities to shape immune responses by promoting IgA production and regulatory T cell development. We have also discovered that imprinting CD103+ intestinal DCs with these capacities is dependent upon local cues from the diet and intestinal epithelium. Ongoing studies will define how antigen delivery and imprinting of intestinal DCs is regulated and the role of these processes in appropriately balancing immune responses in the intestine.

The second body of work investigates the formation and function of a newly appreciated class of intestinal lymphoid tissues, isolated lymphoid follicles (ILFs). ILFs play a crucial role in the protection against potential pathogens, however unlike secondary lymphoid tissues such as Peyer’s patches, ILFs are not preformed, but develop in response to inflammatory stimuli and dietary cues. Understanding how this inducible reservoir of immune inductive sites develops and functions is central to understanding how the mucosal immune system protects from pathogens and will have applications in other conditions where lymphoid tissues form such as chronic inflammatory diseases and malignancy.

Selected Publications:

1 McDonald, K. G. et al. CCR6 Promotes Steady State Intestinal Mononuclear Phagocyte Association with the Intestinal Epithelium, Imprinting, and Immune Surveillance. Immunology, doi:10.1111/imm.12801 (2017).

2 Knoop, K. A. et al. Antibiotics promote the sampling of luminal antigens and bacteria via colonic goblet cell associated antigen passages. Gut microbes, 1-12, doi:10.1080/19490976.2017.1299846 (2017).

3 Knoop, K. A. et al. Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria. Sci Immunol 2, doi:10.1126/sciimmunol.aao1314 (2017).

4 Chai, J. N. et al. Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation. Sci Immunol 2, doi:10.1126/sciimmunol.aal5068 (2017).

5 Knoop, K. A., McDonald, K. G., Kulkarni, D. H. & Newberry, R. D. Antibiotics promote inflammation through the translocation of native commensal colonic bacteria. Gut 65, 1100-U1160, doi:10.1136/gutjnl-2014-309059 (2016).

6 Song, C. et al. Unique and redundant functions of NKp46(+) ILC3s in models of intestinal inflammation. Journal of Experimental Medicine 212, 1869-1882, doi:10.1084/jem.20151403 (2015).

7 Knoop, K. A., McDonald, K. G., McCrate, S., McDole, J. R. & Newberry, R. D. Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon. Mucosal Immunology 8, 198-210, doi:10.1038/mi.2014.58 (2015).

8 Miller, M. J., Knoop, K. A. & Newberry, R. D. Mind the GAPs: insights into intestinal epithelial barrier maintenance and luminal antigen delivery. Mucosal Immunology 7, 452-454, doi:10.1038/mi.2014.4 (2014).

9 McDonald, K. G. et al. Epithelial expression of the cytosolic retinoid chaperone cellular retinol binding protein II is essential for in vivo imprinting of local gut dendritic cells by lumenal retinoids. Am J Pathol 180, 984-997, doi:10.1016/j.ajpath.2011.11.009 (2012).

10 McDole, J. R. et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483, 345-349, doi:10.1038/nature10863 (2012).

Last Updated: 1/12/2018 12:16:06 PM

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