Gundrun Debes, DVM

Gudrun Debes, DVM

Contact Dr. Debes

233 S. Tenth Street
Room 526
Philadelphia, PA 19107

(215) 955-6971

Medical School

DVM, Charité University Medicine, Free University Berlin, Berlin, Germany - 2002

Fellowship

Stanford University School of Medicine, Stanford, CA

Research & Clinical Interests

Effector and memory lymphocytes migrate into extralymphoid tissues as well as sites of inflammation and infection. Subsequently, lymphocytes enter the afferent lymph to reach draining lymph nodes. After a short time period of residency, lymphocytes exit the lymph node via the efferent lymph, which brings them back into the blood. This dynamic process of lymphocyte recirculation, which is tightly regulated at each step, is essential for immune surveillance and defense against pathogens, but it can also contribute to inflammation in autoimmunity, allergy and transplant rejection.

My laboratory seeks to understand the regulation of lymphocyte recirculation as well as the microenvironmental localization of different effector and memory lymphocytes within extralymphoid tissues, especially the skin. It is our long-term goal to advance understanding of T and B cell recirculation and migration pathways leading to novel approaches to manipulate tissue infiltrates. This knowledge will give us the tools to moderate inflammation in inflammatory and autoimmune diseases and to enhance organ-specific immunity.

My laboratory has two main interests:

(1) The signals that mediate T cell retention in vs. egress from the effector site during inflammation.

The work of my lab has substantially contributed to our current knowledge of lymphocyte exit from extralymphoid tissues. Employing a unique combination of mouse and sheep models has enabled us to answer basic questions of lymphocyte trafficking that could not have been answered in either system alone. Afferent lymph cannulation in sheep allows for the analysis of lymphocytes draining specific extralymphoid sites and has led to key discoveries. In the mouse, genetic models and available tools complement our studies in sheep.

Our work discovered that memory/effector T cells egress from extralymphoid tissues during inflammation and infection, and exit receptor requirements change during the course of inflammation (Brown et al. 2010). Importantly, we established a proof-of-principle that the regulation of pro-inflammatory T cell egress from the effector site governs the inflammatory process. We demonstrated that exit receptors can be targeted to modulate T cell dwell time and inflammation at effector sites, revealing T cell tissue egress via lymph as a control point of inflammation and novel potential target of anti-inflammatory therapy (Gomez et al. 2015).

Studies are underway to reveal the mechanism by which different chemoattractant pathways regulate T cell egress and retention over the course of inflammation. Follow-up studies will also validate whether specific exit receptors can be targeted for therapeutic purposes during inflammation or infection. 


(2) B cell trafficking into extralymphoid tissues.

While there are many pro- and anti-inflammatory B cell subsets with both antibody-dependent and –independent effector functions, the routes of B cell migration and their functions in extralymphoid tissues are little defined. Using afferent lymph cannulation in sheep, we discovered that B cells constitutively recirculate through the skin (Geherin et al. 2012), an organ that was assumed to be devoid of B cells. Furthermore, different B cells subsets, including innate-like B cells that produce the anti-inflammatory cytokine IL-10, reside in the skin of humans and mice. Peritoneal IL-10+ B-1 cells, which act as regulatory B cells (Bregs) that suppress inflammation (Nakashima et al. 2010, Maseda et al. 2013), preferentially migrate into the inflamed skin (Geherin et al. 2016).

It is our hypothesis that IL-10+ cutaneous innate-like Bregs fulfill a specialized niche in the regulation of skin inflammation, which we aim to visualize using state-of-the art techniques. Other goals are to determine additional properties of skin B cells and the molecules responsible for their homing into skin. Finally, we will test whether IL-10+ Breg migration into inflamed skin limits cutaneous inflammation in mouse models and validate the significance of our findings in the human system with a main focus on the inflammatory skin disease psoriasis.

References cited:

  • Brown et al. 2010. J. Immunol. 185:4873.
  • Geherin et al. 2012. J. Immunol. 188:1627.
  • Nakashima et al. 2010. J. Immunol. 184:4637
  • Maseda et al. 2013. J. Immunol. 191:2780.
  • Geherin et al. 2016. J. Immunol. 196:2514.