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

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2014 Apr 15

PMID 24729611

Citations 15

Authors

Holly E Ponichtera

Mara G Shainheit

Beiyun C Liu

Raktima Raychowdhury

Bridget M Larkin

Joanne M Russo

D Brenda Salantes

Chao-Qiang Lai

Laurence D Parnell

Tae J Yun

Cheolho Cheong

Stephen C Bunnell

Nir Hacohen

Miguel J Stadecker

Affiliations

Soon will be listed here.

Abstract

In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs are uneven and strain dependent. CBA/J (CBA) mice develop severe hepatic granulomatous inflammation associated with prominent Th17 cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. Such Th17 cells fail to develop in low-pathology C57BL/6 (BL/6) mice, and the reasons for these strain-specific differences in 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 CD209a, a murine homolog of human DC-specific ICAM-3-grabbing nonintegrin, compared with 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 overexpression 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.

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