Journal article
Modulating Toll-like Receptor 7 and 9 Responses as Therapy for Allergy and Autoimmunity
Current allergy and asthma reports, Vol.12(1), pp.8-17
02/2012
DOI: 10.1007/s11882-011-0233-4
PMID: 22086297
Abstract
Type I allergic diseases, such as allergic rhinitis and asthma, depend on allergen-induced T-helper type 2 (Th2) cells and IgE-secreting plasma cells. Fortunately, this harmful immune response can be modified by engaging Toll-like receptor (TLR)7 and TLR9, offering hopes to allergy sufferers. While clinical trials employing synthetic ligands for TLR7 or TLR9 are under way, one can wonder whether TLR7 or TLR9 engagements may trigger inadvertent autoreactivity and/or Th1-/Th17-mediated tissue pathology. To neutralize such danger, we have pioneered the development of potent TLR9 pathway antagonists, inhibitory oligonucleotides (INH-ODNs), which work in a sequence-specific manner. Interestingly, INH-ODNs also have TLR7-inhibitory properties; however, these effects appear to be sequence independent and phosphorothioate backbone dependent. In B cells, co-engagement of the B-cell receptor for antigen and TLR7 or TLR9 may influence how INH-ODNs impose their regulatory effects. INH-ODNs block TLR9 activation by competitively antagonizing ligand binding to proteolytically cleaved C-terminal TLR9 fragment. One may envision future use of INH-ODNs in systemic autoimmune diseases, DNA-mediated sepsis, or other situations in which chronic inflammation results from abnormal TLR7- and/or TLR9-mediated immune activation.
Details
- Title: Subtitle
- Modulating Toll-like Receptor 7 and 9 Responses as Therapy for Allergy and Autoimmunity
- Creators
- Damir Matesic - Indiana Institute of Immunology, Allergy, and Asthma 3611 South Reed Road #107 Kokomo IN 46902 USAAleksander Lenert - Cleveland Clinic 9500 Euclid Avenue Cleveland OH 44195 USAPetar Lenert - Carver College of Medicine, Department of Internal Medicine The University of Iowa C428-2GH, 200 Hawkins Drive Iowa City IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Current allergy and asthma reports, Vol.12(1), pp.8-17
- Publisher
- Current Science Inc
- DOI
- 10.1007/s11882-011-0233-4
- PMID
- 22086297
- ISSN
- 1529-7322
- eISSN
- 1534-6315
- Language
- English
- Date published
- 02/2012
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094217002771
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