April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Dendritic Cell-produced IL-33 Links Microbial Pathogens to Allergic Inflammation
Author Affiliations & Notes
  • De-Quan Li
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX
  • Zhitao Su
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX
    School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China
  • Jing Lin
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX
    Ophthalmology, Affiliated Hospital of Qingdao University Medical College, Qingdao, China
  • Lili Zhang
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX
  • Cintia S. De Paiva
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX
  • Stephen C Pflugfelder
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX
  • Footnotes
    Commercial Relationships De-Quan Li, None; Zhitao Su, None; Jing Lin, None; Lili Zhang, None; Cintia De Paiva, None; Stephen Pflugfelder, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2485. doi:
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      De-Quan Li, Zhitao Su, Jing Lin, Lili Zhang, Cintia S. De Paiva, Stephen C Pflugfelder; Dendritic Cell-produced IL-33 Links Microbial Pathogens to Allergic Inflammation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2485.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Interleukin-33 (IL-33) has been identified as a novel pro-allergic cytokine that initiate Th2-dominant allergic inflammation. Dendritic cells (DCs) are major innate immunity cells; however, it is not clear whether DCs produce IL-33. This study identified a novel mechanism by which DCs links microbial pathogens to allergic inflammation via Toll-like receptor (TLR), NF-κB and IL-33 signaling pathway.

Methods: Mouse bone marrow derived DCs were treated with or without microbial pathogens or recombinant mouse (rm) IL-33. The mRNA expression was determined by reverse transcription and real time PCR, and protein production was evaluated by ELISA, Western blotting, immunofluorescent staining and flow cytometry.

Results: IL-33 mRNA and protein were found to be expressed by DCs and largely induced by specific microbial pathogens, especially lipopolysaccharide (LPS) and flagellin, the ligands to TLR4 and TLR5 respectively. Using a mouse model of topical challenge by LPS and flagellin, IL-33-producing DCs were observed in ocular mucosal surface and the draining cervical lymph nodes. LPS and flagellin were found to promote DC maturation with enhanced expression of CD40, CD80, CD86 and MHC classs II. The increased expression of MyD88, NF-κB1, NF-κB2 and RelA accompanied by NF-κB p65 activation with nuclear translocation was observed in DCs exposed to flagellin. The IL-33 induction by flagellin was significantly blocked by TLR5 antibody or NFκB activation inhibitor quinazoline. When treated with rmIL-33, DCs were activated to express the increased maturation markers CD40 and CD80, stimulated Th2 (IL-4, IL-5 and IL-13) and inflammatory mediators (TNFα, IL-1β and CCL17), as well as OX40L that enables amplification of Th2 cell differentiation. This stimulatory effect of IL-33 in DCs was significantly blocked by ST2 antibody or soluble ST2.

Conclusions: These findings demonstrate that DCs produce IL-33 via TLR/NF-κB signaling pathways, suggesting a molecular mechanism by which local allergic inflammatory response may be amplified by DC-produced IL-33.

Keywords: 490 cytokines/chemokines • 555 immunomodulation/immunoregulation • 637 pathology: experimental  
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