Gregory F Sonnenberg

faculty photo
Research Associate of Medicine
Department: Medicine

Contact information
Room 906 BRB II/III
421 Curie Boulevard
Perelman School of Medicine
Philadelphia, PA 19104-4539
Office: (215) 898-6926
Lab: 938 BRB II/III
B.S. (Biomedical Sciences)
the State University of New York at Buffalo, 2007.
PhD (Immunology)
University of Pennsylvania, 2011.
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Description of Research Expertise

The human immune system is critical to protect against infection with pathogenic microorganisms. However, inappropriate immune responses against our own tissues or non-harmful environmental triggers such as beneficial commensal bacteria that normally colonize the body’s barrier surfaces can promote autoimmune or chronic inflammatory diseases. Indeed, emerging studies in patient populations indicate that abnormal host immune responses to commensal bacteria are either associated with, or causally-linked to, the pathogenesis and progression of numerous chronic infectious, inflammatory and metabolic diseases, including HIV, viral hepatitis, cardiovascular disease, inflammatory bowel disease (IBD), cancer, diabetes and obesity. The focus and long-term research goals of the Sonnenberg Laboratory are to interrogate the mechanisms that regulate normal host immune responses to commensal bacteria and prevent chronic inflammation associated with human disease. Delineating these complex pathways will lead to a better understanding of the pathogenesis of chronic human diseases and direct the future development of novel preventative and therapeutic strategies targeting host-commensal bacteria interactions.

To better understand host-commensal bacteria interactions we have been studying the recently identified populations of intestinal-resident innate lymphoid cells (ILCs). ILCs are an emerging family of immune cells that differentiate, independent of somatic recombination, from IL-7Rα+ Id2-dependent lymphoid progenitors. ILCs share striking similarities to heterogeneous populations of effector T cells. As such, ILCs can currently be broadly classified into 3 groups based on their developmental requirements for specific transcription factors, common activating receptors and expression of effector cytokines. Group 1 ILCs are T-bet+, are activated by IL-18 and IL-12, and express IFNγ. Group 2 ILCs are GATA-3+ and RORα+, are activated by IL-25, IL-33 and TSLP, and express IL-5, IL-9, IL-13 and amphiregulin. Group 3 ILCs are RORγt-dependent, are activated by IL-1β and IL-23, and express IL-22 and IL-17. Importantly, group 3 ILCs have been found to be critical regulators of cytokine-mediated intestinal epithelial cell responses that promote immunity to extracellular bacteria, inflammation and tissue repair in the intestine.

The Sonnenberg Lab has focused extensively on interrogating the role of group 3 RORγt+ ILCs in regulating interactions between intestinal commensal bacteria and the mammalian immune system. In our recent and ongoing research, we have identified populations of group 3 RORγt+ ILCs in the intestinal tissues of healthy humans, non-human primates and mice that play critical roles in regulating host-commensal bacteria relationships via two distinct mechanisms. First, through production of IL-22, ILCs were found to regulate systemic immune cell homeostasis by promoting the anatomical containment of a subset of commensal bacteria that normally resides in the gut-associated lymphoid-tissues of healthy humans, non-human primates and mice. Second, through expression of MHCII, ILCs were found to regulate CD4+ T cell responses to intestinal commensal bacteria and prevent chronic intestinal inflammation. Ongoing research in the Sonnenberg Lab is focused on interrogating functional interactions between ILCs, the adaptive immune system and lymphoid tissue-resident commensal bacteria, and their involvement in health and disease.

We have also recently launched a pioneering translational research effort involving clinical collaborators at Penn, The Children’s Hospital of Philadelphia, the Philadelphia VA Medical Center and other research institutions to examine primary human samples from both healthy individuals and defined patient populations. For example, we have recently identified an association between dysregulated immune responses to Alcaligenes bacteria and disease progression in patients suffering from inflammatory bowl disease or Hepatitis C infection. Our ongoing research will further interrogate ILC responses and interactions with commensal bacteria in healthy and diseased primary human tissue samples. We anticipate that these studies will allow us to directly translate our findings in mouse models to clinically relevant information that may aid in the development of novel therapeutics to prevent or treat chronic human diseases.

Graduate students and talented postdoctoral researchers are encouraged to directly contact Dr Sonnenberg to discuss potential rotation projects and open positions in the laboratory.

*Selected publications

Hepworth M.R., Monticelli L.A., Fung T.C., Ziegler C.G.K., Grunberg S., Sinha R., Mantegazza A.R., Ma H.L., Crawford A., Angelosanto J.M., Wherry E.J., Koni P.A., Bushman F.D., Elson C.O., Eberl G., Artis D., Sonnenberg G.F. (2013) Innate lymphoid cells regulate CD4+ T cell responses to intestinal commensal bacteria. Nature [PMCID: PMC3699860]

Sonnenberg G.F. (2013) New tricks for innate lymphoid cells Journal of Leukocyte Biology [PMCID: in progress]

Sonnenberg G.F., Mjosberg J., Spits H., Artis D. (2013) Snapshot: Innate lymphoid cells. Immunity [PMCID: in progress]

Qiu J., Guo X., Chen Z.E., He L., Sonnenberg G.F., Artis D., Fu Y.X., Zhou L. (2013) Group 3 Innate Lymphoid Cells Inhibit T-Cell-Mediated Intestinal Inflammation through Aryl Hydrocarbon Receptor Signaling and Regulation of Microflora. Immunity [PMCID: in progress]

Yang Q., Monticelli L.A., Saenz S.A., Chi A.W., Sonnenberg G.F., Tang J., De Obaldia M.E., Bailis W., Bryson J., Toscano K., Huang J., Haczku A., Pear W.S., Artis D., Bhandoola A. (2013) T Cell Factor 1 is required for group 2 innate lymphoid cell generation. Immunity [PMCID: in progress]

Kim B.S., Siracusa M.C., Saenz S.A., Noti M., Monticelli L.A., Sonnenberg G.F., Hepworth M.R., Van Voorhees A.S., Comeau M.R., Artis D. (2013) TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Science Translational Medicine [PMCID: PMC3637661]

Osborne L., Joyce K.L., Alenghat T., Sonnenberg G.F., Giacomin P.R., Du Y., Bergstrom K.S., Vallance B.A., Nair M.G. (2013) Resistin-like molecule (RELM) alpha promotes pathogenic Th17 cell responses and bacterial-induced intestinal inflammation. Journal of Immunology [PMCID: PMC3601830]

Sonnenberg G.F. and Artis D. (2012) Innate lymphoid cell interactions with the microbiota: implications for intestinal health and disease. Immunity. [PMCID: PMC3495160]

Sonnenberg G.F., Monticelli L.A., Alenghat T., Fung T.C., Hutnick N.A., Kunisawa J., Shibata N., Grunberg S., Sinha R., Zahm A.M., Tardif M.R., Sathaliyawala T., Kubota M., Farber D.L., Collman R.G., Shaked A., Fouser L.A., Weiner D.B., Tessier P.A., Friedman J.R., Kiyono H., Bushman F.D., Chang K.M., Artis D. (2012) Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science [PMCID: PMC3659421]

Abt M.C., Osborne L.C., Monticelli L.A., Doering T.A., Alenghat T., Sonnenberg G.F., Paley M.A., Antenus M., Williams K.L., Erikson J., Wherry E.J., Artis D. (2012) Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity [PMCID: PMC3679670]

Monticelli L.A., Sonnenberg G.F., Abt M.C., Alenghat T., Ziegler C.G.K., Doering T.A., Angelosanto J.M., Laidlaw B.J., Yang C.Y., Sathaliyawala T., Kubota M., Tuner D., Diamond J.M., Goldrath A.W., Farber D.L., Collman R.G., Wherry E.J., Artis D. (2011) Innate lymphoid cells promote lung tissue homeostasis following acute influenza virus infection. Nature Immunology [PMCID: PMC3320042]

Sonnenberg G.F., Fouser L.A., Artis, D. (2011) Border Patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nature Immunology. [PMID: 21502992]

Sonnenberg G.F., Monticelli L.A., Elloso M.M., Fouser L.A., Artis D. (2011) CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity [PMCID: PMC3035987]

Sonnenberg G.F., Nair M.G., Kirn T.J., Zaph C., Fouser L.A., Artis D. (2010) Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. Journal of Experimental Medicine [PMCID: PMC2882840]
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Last updated: 09/06/2013
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