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Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V

Vijayanand, P., Seumois, Gregory, Simpson, Laura, Abdul-Wajid, Sarah, Baumjohann, Dirk, Panduro, Marisella, Huang, Xiaozhu, Interlandi, Jeneen, Djuretic, Ivana, Brown, Daniel, Sharpe, Arlene, Rao, Anjana and Ansel, Mark (2012) Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V Immunity, 36, (2), pp. 175-187. (doi:10.1016/j.immuni.2011.12.014).

Record type: Article


FollicularhelperT cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical Thelper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that hypersensitivitysiteV (HS V; also known as CNS2), a 3? enhancer in the Il4 locus, is essential for IL-4production by Tfh cells. Mice lacking HS V display marked defects in type 2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation and increased accessibility of the Il4 promoter. Thus, Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of allergic diseases

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Published date: 24 February 2012
Organisations: Cancer Sciences


Local EPrints ID: 343054
ISSN: 1097-4180
PURE UUID: f48b8fce-6835-4990-b363-9f702ba1ba0d

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Date deposited: 21 Sep 2012 12:20
Last modified: 18 Jul 2017 05:25

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Author: P. Vijayanand
Author: Gregory Seumois
Author: Laura Simpson
Author: Sarah Abdul-Wajid
Author: Dirk Baumjohann
Author: Marisella Panduro
Author: Xiaozhu Huang
Author: Jeneen Interlandi
Author: Ivana Djuretic
Author: Daniel Brown
Author: Arlene Sharpe
Author: Anjana Rao
Author: Mark Ansel

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