Lauren A Zenewicz, PhDDr. Zenewicz

Assistant Professor

2004, University of Pennsylvania, Philadelphia, PA

Postdoctoral Fellow:
Yale University, New Haven, CT

Research Interests:
Inflammation, mucosal immunology, cytokines


BMSB 1034


Research Emphasis

Interleukin-22 (IL-22) is an important cytokine for modulating tissue responses during inflammation. The molecule is highly expressed in patients with chronic inflammatory diseases, such as inflammatory bowel disease, psoriasis and rheumatoid arthritis. Inflammatory signals induce IL-22 expression in activated CD4 T cells and group 3 innate lymphocytes (ILC3s). IL-22 is critical in barrier function, especially in the gastrointestinal tract. We have shown that IL-22 is protective during models of acute colitis, but is immunopathogenic during chronic colitis. IL-22 can also have effects on the host microbiota, causing changes in flora composition that can lead to exacerbated colitis. In addition, IL-22 plays tumorigenic and tumor-protective roles in colorectal cancer, depending on the stage of carcinogenesis. Work from other investigators has shown that IL-22 also has beneficial or harmful functions in other inflamed tissues, such as those of the skin, joints or lungs. As a dual-natured cytokine it is important that its biological activity be tightly regulated in order to limit IL-22 expression to the sites of inflammation. We are currently investigating the role of environmental factors in the regulation of IL-22 expression, as well as a secreted regulatory protein, IL-22 binding protein, that binds to IL-22 with greater affinity than the IL-22 receptor and inhibits IL-22 activity. These studies will expand our knowledge of IL-22, allowing for the effective use of the cytokine in therapeutics for inflammatory diseases.

Current Laboratory Personnel:

Alisha Chitrakar, M.S. Research Assistant I

​Rosemary Pope, Research Technician

Selected Publications:

Zenewicz, L.A., G.D. Yancopoulos, D.M. Valenzuela, A.J. Murphy, M. Karow and R.A. Flavell.  2007.  Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation.  Immunity.  27(4):647-659.

Zenewicz, L.A., G.D. Yancopoulos, D.M. Valenzuela, A.J. Murphy, S. Stevens and R.A. Flavell.  2008.  Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease.  Immunity.  29(6):947-957.

Zenewicz, L.A. and R. A. Flavell.  2008. Interleukin-22 and inflammation: Leukin’ through a glass onion.  European Journal of Immunology.  32(12):3265-3268.

Zenewicz, L.A., A. Antov and R.A. Flavell.  2009.  CD4 T cell differentiation and inflammatory bowel disease.  Trends in Molecular Medicine.  15(5):199-207.

O’Connor, Jr., W.O., L.A. Zenewicz and R.A. Flavell.  2010.  The dual-nature of Th17 cells: Shifting the focus to function.  Nature Immunology.  11(6):471-476.

Kamanaka, M.*, S. Huber*, L.A. Zenewicz*, N. Gagliani, W. O’Conner, Jr., Y.Y. Wan, S. Nakae, Y. Iwakura, L. Hao and R.A. Flavell.  2011.  Memory/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22 dependent intestinal pathology.  The Journal of Experimental Medicine.  208(5): 1027-1040.   *equal contribution

Zenewicz, LA. and R.A. Flavell.  2011.  Recent Advances in Interleukin-22 Biology. International Immunology. 23(3):159-163.

Huber, S., N. Gagliani, L.A. Zenewicz, F. J. Huber, L. Bosurgi, B. Hu, M. Hedi, W. Zhang, W. O’Connor, Jr., A.J. Murphy, D.M. Valenzuela, G.D. Yancopoulos, C. Booth, J.H. Cho, W. Ouyang, C. Abraham and R.A. Flavell.  2012.  IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.  Nature.  491:259-263.

Zenewicz, L.A., X. Yin, G. Wang, E. Elinav, L. Hao, L. Zhao and R.A. Flavell.  2013.  Interleukin-22 deficiency alters colonic microbiota to be transmissible and colitogenic.  Journal of Immunology. 190(10): 5306-5312.

Budda, S.A., A. Girton, J.G. Henderson and
L.A. Zenewicz. 2016. The transcription factor HIF-1α controls expression of the cytokine IL-22 in CD4 T cells. Journal of Immunology. 197:2646-2652.

Budda, S.A., K. Bhattarai, J.L. Alexander and L.A. Zenewicz. Hypoxic modulation of hepatocyte responses to the cytokine interleukin-22 (IL-22). Immunology & Cell Biology.