Id2 Expression Delineates Differential Checkpoints in the Genetic Program of CD8α+ and CD103+ Dendritic Cell Lineages

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2011 May 19

PMID 21587207

Citations 76

Authors

Jacob T Jackson

Yifang Hu

Ruijie Liu

Frederick Masson

Angela DAmico

Sebastian Carotta

Annie Xin

Mary J Camilleri

Adele M Mount

Axel Kallies

Li Wu

Gordon K Smyth

Stephen L Nutt

Gabrielle T Belz

Affiliations

Soon will be listed here.

Abstract

Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8α(+) and CD103(+) DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103(+) and CD8α(+) lineages. Notably, CD103(+) DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-α(-) DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP(+) DCs. It did not restore cross-presenting capacity to Batf3(-/-) or CD103(-)Sirp-α(-)DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses.

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