Faculty
Dr. Kevan Roberts
Associate Professor
Deputy Director, Center for Environmental Health Sciences
kevan.roberts@umontana.edu
Phone (406) 243-4034
Kevan Roberts completed his undergraduate work in Biochemistry at the University of Manchester, UK. He subsequently received his PhD in Immunology under the supervision of Dr. Michael Moore in 1984 while at the Christie Hospital, Manchester, UK. He then completed post-doctoral studies in the Surgery Branch (with Dr. Michael Lotze) and the Laboratory of Immunology (with Dr. Ethan Shevach) at the National Institute of Health, Bethesda, USA and finally the Babraham Institute, Cambridge, UK (with Dr. Peter Kilshaw). He became a Senior Lecturer in Immunology in 1993 at the School of Medicine in Southampton, UK and moved to the University of Montana as an Associate Professor in 2003.
The Roberts lab group. From left: Research Specialist Maria Ferrini, Dr. Kevan Roberts, Graduate Student Teri Girtsman, and Postdoctoral Fellow Zeina Jaffar.
Research Statement
Senior Candidate Teri Girtsman using the FACS- ARIA.
Allergic asthma is characterized by airway hyperresponsiveness and eosinophilic inflammation mediated by CD4+ Th2 cells. Recent studies have also shown that CD4+ Th17 cells also contribute to the inflammatory processes in this disease. That chronic inflammation arises as a consequence of a defect in immune regulation is implied from the observation that lung mucosal immune responses are normally tightly regulated. However, the specific mechanisms that transpire to resolve, or possibly prevent, airway mucosal Th2 and Th17-mediated inflammation are poorly understood. To resolve this issue, our laboratory focuses primarily on the regulation of lung mucosal Th2 and Th17 responses. We are currently elucidating how prostanoids generated during allergic pulmonary inflammation, such as PGI2, serve to selectively limit the progression of Th2 responses and influence antibody production. In addition, we are investigating the effectiveness of natural CD4+CD25+ Foxp3+ regulatory T cells (nTregs) in limiting Th2 and Th17-mediated airway inflammation. Undoubtedly, a better understanding of the regulation of these responses will provide better insight into design of novel approaches to modulate the chronic airway inflammation evident in bronchial asthma.
Research Specialist Maria Martin pipetting - part of the
process of cell harvesting.
A second area of study is the determination of how lung inflammatory responses are exacerbated by inhaled environmental agents. Inhalation of ozone, a commonly encountered environmental pollutant, has been associated with adverse health effects and morbidity in human populations. The ozone-induced airway inflammatory response has been shown to be associated with the release of IL-17 into the airway. We have developed a model of Th17-mediated lung mucosal inflammation in order to investigate several aspects of innate and adaptive immunity that are activated during Th17-induced inflammation and determine how these responses are affected by ozone inhalation. We observed that the most salient features of the Th17 response in the lung included recruitment of B cells and increased transport of secretory immunoglobulins IgA and IgM into the airway. Antigen-specific CD4+ nTregs suppressed the Th17-mdiated inflammation by promoting immune regulation that was restricted to the lung mucosal site. We plan to dissect the mechanisms by which nTregs mediate such immunosuppression and whether they act on the dendritic cells present in the airway. Our long-term aim is to determine the mechanisms by which Th17 cells promote lung mucosal immunity and how the inflammatory process is regulated. These studies will facilitate understanding how these responses prevent colonization of the airway by certain respiratory pathogens and help explain underlying inflammatory processes that contribute to the detrimental health effects of ozone exposure.
Recent Publications
Jaffar Z., Ferrini M.E., Girtsman T.A., and Roberts K. Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B cell recruitment and polymeric IgA and IgM levels in the airways. Euro. J. Immunology, 2009 (in press).
Girtsman T.A., Jaffar Z., Ferrini M.E. and Roberts K. Suppression of Th17- but not Th1- or Th2-mediated pulmonary inflammation by natural CD4+Foxp3+ regulatory T cells. Clinical Experimental Immunol., 2009 (in press).
Jaffar Z., Ferrini M.E., Herritt L.A., and Roberts K. Cutting Edge: Lung Mucosal Th17-Mediated Responses Induce Polymeric Ig Receptor Expression by the Airway Epithelium and Elevate Secretory IgA Levels. J. Immunol., 2009, 182: 4507–4511. NIHMSID : 134711.
Jaffar Z., Ferrini M.E., Buford M.C., Fitzgerald G.A., Roberts K. Prostaglandin I2-IP signaling blocks allergic pulmonary inflammation by preventing recruitment of CD4+ Th2 cells into the airways in a mouse model of asthma. J. Immunol., 2007, 179:6193-203. PMID: 17947695.