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CD209a Expression on Dendritic Cells is Critical for the Development of Pathogenic Th17 Cell Responses in Murine Schistosomiasis1

In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs is uneven and strain dependent. CBA mice develop severe hepatic granulomatous inflammation associated with prominent T helper 17 (Th17) cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23...

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Published in:The Journal of immunology (1950) 2014-04, Vol.192 (10), p.4655-4665
Main Authors: Ponichtera, Holly E., Shainheit, Mara G., Liu, Beiyun C., Raychowdhury, Raktima, Larkin, Bridget M., Russo, Joanne M., Salantes, D. Brenda, Lai, Chao-Qiang, Parnell, Laurence D., Yun, Tae J., Cheong, Cheolho, Bunnell, Stephen C., Hacohen, Nir, Stadecker, Miguel J.
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container_end_page 4665
container_issue 10
container_start_page 4655
container_title The Journal of immunology (1950)
container_volume 192
creator Ponichtera, Holly E.
Shainheit, Mara G.
Liu, Beiyun C.
Raychowdhury, Raktima
Larkin, Bridget M.
Russo, Joanne M.
Salantes, D. Brenda
Lai, Chao-Qiang
Parnell, Laurence D.
Yun, Tae J.
Cheong, Cheolho
Bunnell, Stephen C.
Hacohen, Nir
Stadecker, Miguel J.
description In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs is uneven and strain dependent. CBA mice develop severe hepatic granulomatous inflammation associated with prominent T helper 17 (Th17) cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. Such Th17 cells fail to develop in low-pathology BL/6 mice, and the reasons for these strain-specific differences in antigen (Ag) presenting cell (APC) reactivity to eggs remain unclear. We show by gene profiling that CBA DCs display an 18-fold higher expression of the C-type lectin receptor (CLR) CD209a, a murine homologue of human DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), than BL/6 DCs. Higher CD209a expression was observed in CBA splenic and granuloma APC subpopulations, but only DCs induced Th17 cell differentiation in response to schistosome eggs. Gene silencing in CBA DCs, and over-expression in BL/6 DCs, demonstrated that CD209a is essential for egg-elicited IL-1β and IL-23 production and subsequent Th17 cell development, which is associated with SRC, RAF-1, and ERK1/2 activation. These findings reveal a novel mechanism controlling the development of Th17 cell-mediated severe immunopathology in helminthic disease.
doi_str_mv 10.4049/jimmunol.1400121
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title CD209a Expression on Dendritic Cells is Critical for the Development of Pathogenic Th17 Cell Responses in Murine Schistosomiasis1
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