Study Identifies Regulators of Eosinophilic Inflammation in Inflammatory Bowel Disease
Simon P. Hogan, PhD, Research Director for our Division, identified a new role for the innate inflammatory cell macrophage and NFkB signaling pathway in the regulation of eosinophilic inflammation in inflammatory bowel disease (IBD). Employing a murine model of colitis and mice with NFkB signaling deleted selectively in macrophages, Hogan identified a requirement for NFkB signaling in inflammatory macrophages for secretion of the eosinophil-selective chemokine CCL11, eosinophilic inflammation and the histopathology of experimental colitis (DSS-induced model). Molecular and cellular analyses revealed a link between expression of calprotectin (S100a8/S100a9), Ccl11expression and eosinophil numbers in the DSS-treated colon. The results indicate that myeloid cell–specific NF-kB-dependent pathways play an unexpected role in CCL11 expression and maintenance of eosinophilic inflammation in experimental colitis. These data were published in the Journal of Immunology and indicate that targeting myeloid cells and NFkB-dependent pathways may be of therapeutic benefit for the treatment of eosinophilic inflammation and histopathology in IBD.
Method Developed to Directly Evaluate Eosinophil Tracking In Vivo
Most in vivo studies of granulocytes draw conclusions about their trafficking based on examination of their steady-state tissue/blood levels, which result from a combination of tissue homing, survival and egress rather than direct examination of cellular trafficking. Ting Wen, PhD, and Marc Rothenberg, MD, PhD, Division Director, developed a unique cell transfer system involving the adoptive transfer of a genetically labeled, bone-marrow-derived unique granulocyte population (eosinophils) into an elicited inflammatory site, the allergic lung. As published in the Proceedings of the National Academy of Sciences, a dual polychromatic FACS-based biomarker-labeling system based on the IL4-eGFP transgene (4get) or Cd45.1 allele was used to track IV-transferred eosinophils into the airway following allergen or T(H)2-associated stimuli in the lung in multiple mouse strains. The system was amenable to reverse tagging of recipients, thus allowing transfer of nonlabeled eosinophils and competitive tracking of multiple populations of eosinophils in vivo. This unique eosinophil transfer system provides an unprecedented opportunity to examine airway eosinophil migration without the need for extensive efforts to acquire donor source and time-consuming genetic crossing and has already been used to identify a long eosinophil half-life in the allergic lung and a definite role for ST2 in regulating eosinophil trafficking.
Faculty Recognized For Research Endeavors
The American College of Allergy, Asthma & Immunology (ACAAI) unanimously voted Amal Assa'ad, MD, the Clinical Director, to receive the ACAAI Woman in Allergy Award for 2013. This prestigious award recognizes her dedication in advancing the specialty by her work in food allergy and science. Recently appointed faculty member Patricia Fulkerson, MD, PhD, was awarded a 2013 ARTrustTM Faculty Development Award by the American Academy of Allergy, Asthma and Immunology (AAAAI) for her eosinophil progenitor research. This is the academy’s most prestigious award. The funding supports Fulkerson’s research investigating the regulation of eosinophil progenitors by Toll-like receptors, which may support development of therapeutics for eosinophil-associated disorders such as asthma and eosinophilic gastrointestinal disorders. Recently appointed faculty member Joseph Sherrill, PhD, was awarded the Thrasher Research Fund Early Career Award in recognition of his promise as an investigator. His work employs a functional genomics approach to understand the genetic etiology of inflammatory diseases such as eosinophilic gastrointestinal disorders.