P145 Innate immune activation through ITAM-Syk-CARD9 signaling coupling to inflammasome is essential for the development of contact allergy to organic chemical allergens
In: Cytokine, Jg. 59 (2012-09-01), S. 566-567
Online
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Zugriff:
Introduction Allergic contact dermatitis (ACD) is a major cause of occupational skin diseases and is caused by T cells sensitized previously to contact allergens. One of the clinically most important categories of contact allergens are small organic molecule that are chemically reactive (chemical sensitizers). Although the sensitization process of T cells requires activation of skin dendritic cells (DCs) by chemical sensitizers, it is unclear how the sensitizers activate the innate immune system. CARD9 is an essential adaptor protein regulating NF-κB activation and inflammatory cytokine production through tyrosine-based activation motif (ITAM)-coupled receptors and the tyrosine kinase Syk on myeloid cells, and is known as a crucial molecule in the innate activation pathway for antifungal defense. However its role in allergic diseases is unknown. Methods Contact hypersensitivity (CHS) to trinitrochlorobenzene (TNCB) was sensitized by painting TNCB on skin in mice lacking MyD88 or ITAM-associated signaling molecules, or by injection of TNBS (a water-soluble form of TNCB)-modified bone marrow-derived dendritic cells (BMDCs) from the knockout mice. Elicitation and evaluation of CHS response (ear swelling, histology and the development of TNCB-specific T cells) was performed on day 5. In addition, cytokine productions and signaling activation in response to various contact sensitizers in BMDCs from the knockout mice were examined Results Expression of CARD9 in DCs and that of MyD88 in T cells are both required for sensitization of CHS to TNCB. IL-1R-MyD88-mediated signaling in T cells was required for sensitizer-activated DCs to generate TNCB-reactive T cells producing IL-17. On the other hand, activation of the signaling pathway through the ITAM-containing adaptor DAP12 and Syk was essential for ROS generation and NLRP3-dependent Caspase-1 activation induced by TNBS stimulation in DCs. Although the CARD9/BCL10 signaling was dispensable for the inflammasome activation, it was essential for contact sensitizer-indueced pro-IL-1β synthesis in DCs through NF-κB activation. In addition, we found that all contact sensitizers tested (FITC, Oxazolone and DNFB) could induce Syk activation, and that the ROS production, Caspase-1 activation and IL-1β production induced by these sensitizers were all dependent on Syk and the pro-IL-1β synthesis through NF-κB activation was all dependent on CARD9. Conclusion The ability to induce the Syk-mediated ROS production coupling to NLRP3 inflammasome activation and the CARD9-mediated NF-κB activation leading to pro-IL-1β synthesis may be a common characteristic of chemical contact sensitizers that is required for skin DCs to sensitize T cells through the IL-1β-IL-1R pathway.
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P145 Innate immune activation through ITAM-Syk-CARD9 signaling coupling to inflammasome is essential for the development of contact allergy to organic chemical allergens
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Autor/in / Beteiligte Person: | Yoshida, Hiroki ; Yasukawa, S. ; Hara, Hiromitsu ; Furue, Masutaka |
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Zeitschrift: | Cytokine, Jg. 59 (2012-09-01), S. 566-567 |
Veröffentlichung: | Elsevier BV, 2012 |
Medientyp: | unknown |
ISSN: | 1043-4666 (print) |
DOI: | 10.1016/j.cyto.2012.06.245 |
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