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

Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V
Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V
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
1097-4180
175-187
Vijayanand, P.
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Simpson, Laura
f2a9084e-9ef7-454b-a658-5d9ecf742a3a
Abdul-Wajid, Sarah
98ba63ed-3212-44af-a055-12226e0e6e50
Baumjohann, Dirk
1e713aa9-2965-4d4c-8118-b3684c32e5c4
Panduro, Marisella
a1cc0bcd-7231-4412-b756-8f7aa2fcdf44
Huang, Xiaozhu
0b6d8f8d-7bfd-4bd5-9b5c-adc95b464b41
Interlandi, Jeneen
e7f2b5a9-4fce-4389-989c-3703a5ef5e4a
Djuretic, Ivana
89249b39-5304-4c61-91d3-452e9c07e4e6
Brown, Daniel
25c3633f-4d46-4b95-855e-4b57b180d320
Sharpe, Arlene
c233bb13-7275-4240-953f-0990acfc374f
Rao, Anjana
d22da889-4e55-4fb5-9818-bd47dc12348a
Ansel, Mark
7bfd7958-c1c5-4e95-b472-bf3e6d24eb18
Vijayanand, P.
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Simpson, Laura
f2a9084e-9ef7-454b-a658-5d9ecf742a3a
Abdul-Wajid, Sarah
98ba63ed-3212-44af-a055-12226e0e6e50
Baumjohann, Dirk
1e713aa9-2965-4d4c-8118-b3684c32e5c4
Panduro, Marisella
a1cc0bcd-7231-4412-b756-8f7aa2fcdf44
Huang, Xiaozhu
0b6d8f8d-7bfd-4bd5-9b5c-adc95b464b41
Interlandi, Jeneen
e7f2b5a9-4fce-4389-989c-3703a5ef5e4a
Djuretic, Ivana
89249b39-5304-4c61-91d3-452e9c07e4e6
Brown, Daniel
25c3633f-4d46-4b95-855e-4b57b180d320
Sharpe, Arlene
c233bb13-7275-4240-953f-0990acfc374f
Rao, Anjana
d22da889-4e55-4fb5-9818-bd47dc12348a
Ansel, Mark
7bfd7958-c1c5-4e95-b472-bf3e6d24eb18

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), 175-187. (doi:10.1016/j.immuni.2011.12.014).

Record type: Article

Abstract

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

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Local EPrints ID: 343054
URI: http://eprints.soton.ac.uk/id/eprint/343054
ISSN: 1097-4180
PURE UUID: f48b8fce-6835-4990-b363-9f702ba1ba0d
ORCID for P. Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723

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Date deposited: 21 Sep 2012 12:20
Last modified: 14 Mar 2024 11:58

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Contributors

Author: P. Vijayanand ORCID iD
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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