LAB/NTAL regulates zymosan-mediated inflammatory responses in Bone Marrow Derived Dendritic Cells (BMDC) (98.14)
| Autor: | Selinda Orr, Laura Quigley, Stephen Roessler, Deborah Hodge, Catherine Razzook, Marco Cardone, Weiguo Zhang, Giorgio Trinchieri, Lyudmila Lyakh, Daniel McVicar |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:98.14-98.14 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.184.supp.98.14 |
| Popis: | Immune sensing of fungi occurs via multiple pathogen recognition receptors such as Dectin-1/2, mannose receptor and TLR2. The β-glucans and mannans in fungal cell walls activate these receptors. Stimulation of DCs via TLR2 results in the production of IL-10 and little IL-12, while Dectin-1 utilizes a hemi-ITAM (immunoreceptor tyrosine based activation motif) and Syk to facilitate IL-23 production leading to Th17 polarization. We have recently shown that the linker for activation of B cells/Non-T cell activating linker (LAB/NTAL), a known regulator of ITAM-mediated signaling, is expressed in BMDCs. Here we examine whether LAB regulates the response of BMDC to zymosan by affecting Dectin-1 signaling. We find that LAB, Syk, Cbl, MAPK and Akt are rapidly and transiently phosphorylated following zymosan stimulation. Moreover, zymosan stimulated Lat2-/- BMDC produced decreased IL-10 and IL-12p40 and increased TNF levels suggesting the involvement of LAB in regulating BMDC cytokine production. Unexpectedly, direct engagement of Dectin-1 by purified β-glucans failed to elicit LAB phosphorylation. Interestingly, water-soluble components of zymosan induced phosphorylation of FcRγ, Syk, and LAB. Indeed, purified yeast-derived mannans also stimulated phosphorylation of Syk and LAB in BMDC. These data indicate that LAB regulates the BMDC inflammatory response to fungal pathogens not by affecting Dectin-1 signaling but by regulating mannan-derived signals likely through Dectin-2. |
| Databáze: | OpenAIRE |
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