Th2 cytokine responses are required for immunity to helminth parasites and are also responsible for the detrimental inflammation associated with allergies and asthma. Given the global prevalence of soil transmitted helminth infections, currently estimated at two billion individuals worldwide, coupled with the pandemic of allergic diseases in industrialized countries, it is critical to gain a better understanding of the pathways that control Th2 cytokine-mediated immunity and inflammation. Despite significant developments in our understanding of the pathways that control the differentiation and regulation of Th2 immunity, the innate immune cells that recognize helminth- or allergen-derived antigens and present them to naive CD4+ T cells remain poorly defined.
The aims of this proposal are directed at better understand those cells and mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI085828-03
Application #
8215616
Study Section
Special Emphasis Panel (ZRG1-F07-K (20))
Program Officer
Wali, Tonu M
Project Start
2010-03-05
Project End
2013-03-04
Budget Start
2012-03-05
Budget End
2013-03-04
Support Year
3
Fiscal Year
2012
Total Cost
$53,942
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hill, D A; Siracusa, M C; Ruymann, K R et al. (2014) Omalizumab therapy is associated with reduced circulating basophil populations in asthmatic children. Allergy 69:674-7
Osborne, Lisa C; Monticelli, Laurel A; Nice, Timothy J et al. (2014) Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science 345:578-82
Noti, Mario; Kim, Brian S; Siracusa, Mark C et al. (2014) Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis. J Allergy Clin Immunol 133:1390-9, 1399.e1-6
Kim, Brian S; Wang, Kelvin; Siracusa, Mark C et al. (2014) Basophils promote innate lymphoid cell responses in inflamed skin. J Immunol 193:3717-25
Noti, Mario; Wojno, Elia D Tait; Kim, Brian S et al. (2013) Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med 19:1005-13
Saenz, Steven A; Siracusa, Mark C; Monticelli, Laurel A et al. (2013) IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells. J Exp Med 210:1823-37
Kim, Brian S; Siracusa, Mark C; Saenz, Steven A et al. (2013) TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci Transl Med 5:170ra16
Hill, David A; Siracusa, Mark C; Abt, Michael C et al. (2012) Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18:538-46
Siracusa, Mark C; Saenz, Steven A; Hill, David A et al. (2011) TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477:229-33
Siracusa, Mark C; Comeau, Michael R; Artis, David (2011) New insights into basophil biology: initiators, regulators, and effectors of type 2 inflammation. Ann N Y Acad Sci 1217:166-77