While much is known about the induction of the inflammatory response in allergic inflammation, far less is understood about endogenous mechanisms that naturally down- regulate allergic inflammatory responses. These endogenous responses could potentially be harnessed to develop novel anti-inflammatory therapies for hypersensitivity diseases. In this proposal we propose to investigate the role that activation of Siglec-F (Sialic acid-binding Ig-superfamily lectin-F) cell surface receptors play in down-regulating the inflammatory, and tissue remodeling response in allergic inflammation. Siglec-F is highly expressed on cells associated with allergic inflammation such as eosinophils. A functional role for Siglec-F receptors in regulating allergic responses is suggested from the presence in their cytoplasmic tails of ITIM motifs know to be involved in inhibitory signaling pathways in the immune system. We therefore propose to determine 1) the mechanisms by which Siglec-F exerts this anti-allergic effect in vivo and in vitro, and 2) identify and characterize ligands specific for Siglec-F that may be generated by epithelium during an allergic inflammatory response in vivo, (as their name implies Siglecs bind to ligands expressing the glycan sialic acid), and 3) characterize the expression of Siglec-8 (the human orthologue of mouse Siglec-F) and its ligand at sites of eosinophilic inflammation in humans with asthma. Narrative This proposal will increase our understanding of how a protein Siglec-F may stop the allergic response in a model of allergic inflammation. An improved understanding of how Siglec-F stops the allergic response may provide insight into the development of new therapies for individuals with ongoing chronic allergic inflammation to stop the allergic inflammatory response and thus stop continued allergy symptoms.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section (HAI)
Program Officer
Dong, Gang
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
Zip Code
Doherty, Taylor A; Broide, David H (2017) Pathways to limit group 2 innate lymphoid cell activation. J Allergy Clin Immunol 139:1465-1467
Eastman, Jacqueline J; Cavagnero, Kellen J; Deconde, Adam S et al. (2017) Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 140:101-108.e3
Miller, Marina; Rosenthal, Peter; Beppu, Andrew et al. (2017) Oroscomucoid like protein 3 (ORMDL3) transgenic mice have reduced levels of sphingolipids including sphingosine-1-phosphate and ceramide. J Allergy Clin Immunol 139:1373-1376.e4
Kim, Alexander S; Doherty, Taylor A; Karta, Maya R et al. (2016) Regulatory B cells and T follicular helper cells are reduced in allergic rhinitis. J Allergy Clin Immunol 138:1192-1195.e5
Rajan, Jessica; Newbury, Robert O; Anilkumar, Arjun et al. (2016) Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids. J Allergy Clin Immunol 137:147-156.e8
Das, Sudipta; Miller, Marina; Beppu, Andrew K et al. (2016) GSDMB induces an asthma phenotype characterized by increased airway responsiveness and remodeling without lung inflammation. Proc Natl Acad Sci U S A 113:13132-13137
Zhou, Weisong; Toki, Shinji; Zhang, Jian et al. (2016) Prostaglandin I2 Signaling and Inhibition of Group 2 Innate Lymphoid Cell Responses. Am J Respir Crit Care Med 193:31-42
Rawson, Renee; Yang, Tom; Newbury, Robert O et al. (2016) TGF-?1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. J Allergy Clin Immunol 138:791-800.e4
Rawson, Renee; Anilkumar, Arjun; Newbury, Robert O et al. (2015) The TGF?1 Promoter SNP C-509T and Food Sensitization Promote Esophageal Remodeling in Pediatric Eosinophilic Esophagitis. PLoS One 10:e0144651
Doherty, T A; Broide, D H (2015) Group 2 innate lymphoid cells: new players in human allergic diseases. J Investig Allergol Clin Immunol 25:1-11; quiz 2p following 11

Showing the most recent 10 out of 50 publications