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The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells

The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells
The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells
Dendritic cells (DCs) link innate and adaptive immunity, initiating and regulating effector cell responses. They ubiquitously express members of the LILR (ILT, LIR, CD85) family of molecules, some of which recognize self-HLA molecules, but little is known of their possible functions in DC biology. We demonstrate that the inhibitory receptor LILRB1 (ILT2, LIR1, CD85j) is selectively up-regulated during DC differentiation from monocyte precursors in culture. Continuous ligation of LILRB1 modulated cellular differentiation, conferred a unique phenotype upon the resultant cells, induced a profound resistance to CD95-mediated cell death, and inhibited secretion of cytokines IL-10, IL-12p70, and TGF-beta. These features remained stable even after exposure of the cells to bacterial LPS. Ligated DCs exhibited poor stimulatory activity for primary and memory T-cell proliferative responses, but this was substantially reversed by blockade of CD80 or its preferred ligand CTLA-4, or by depleting CD4(+) CD25(+) CD127(lo) regulatory T cells. Our findings suggest that ligation of LILRB1 on DCs by self-HLA molecules may play a key role in controlling the balance between the induction and suppression of adaptive immune responses.
0006-4971
3090-3096
Young, Neil T.
420c5bc3-494e-4840-9af2-dc1b081291b1
Waller, Edward C.P.
76eb0f3e-8f74-4f20-a837-2e7eaddde7a7
Patel, Rashmi
8937a61f-afec-41ee-81cb-e8442e81c9f7
Roghanian, Ali
e2b032c2-60a0-4522-a3d8-56a768792f36
Austyn, Jonathan M.
bbf7bdb1-ad81-4dda-8a3c-c3320ba858f7
Trowsdale, John
5bbacc4a-45f4-4376-8357-a7c79fc4fe12
Young, Neil T.
420c5bc3-494e-4840-9af2-dc1b081291b1
Waller, Edward C.P.
76eb0f3e-8f74-4f20-a837-2e7eaddde7a7
Patel, Rashmi
8937a61f-afec-41ee-81cb-e8442e81c9f7
Roghanian, Ali
e2b032c2-60a0-4522-a3d8-56a768792f36
Austyn, Jonathan M.
bbf7bdb1-ad81-4dda-8a3c-c3320ba858f7
Trowsdale, John
5bbacc4a-45f4-4376-8357-a7c79fc4fe12

Young, Neil T., Waller, Edward C.P., Patel, Rashmi, Roghanian, Ali, Austyn, Jonathan M. and Trowsdale, John (2008) The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells. Blood, 111 (6), 3090-3096. (doi:10.1182/blood-2007-05-089771). (PMID:18094328)

Record type: Article

Abstract

Dendritic cells (DCs) link innate and adaptive immunity, initiating and regulating effector cell responses. They ubiquitously express members of the LILR (ILT, LIR, CD85) family of molecules, some of which recognize self-HLA molecules, but little is known of their possible functions in DC biology. We demonstrate that the inhibitory receptor LILRB1 (ILT2, LIR1, CD85j) is selectively up-regulated during DC differentiation from monocyte precursors in culture. Continuous ligation of LILRB1 modulated cellular differentiation, conferred a unique phenotype upon the resultant cells, induced a profound resistance to CD95-mediated cell death, and inhibited secretion of cytokines IL-10, IL-12p70, and TGF-beta. These features remained stable even after exposure of the cells to bacterial LPS. Ligated DCs exhibited poor stimulatory activity for primary and memory T-cell proliferative responses, but this was substantially reversed by blockade of CD80 or its preferred ligand CTLA-4, or by depleting CD4(+) CD25(+) CD127(lo) regulatory T cells. Our findings suggest that ligation of LILRB1 on DCs by self-HLA molecules may play a key role in controlling the balance between the induction and suppression of adaptive immune responses.

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e-pub ahead of print date: 19 December 2007
Published date: 15 March 2008
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 369612
URI: https://eprints.soton.ac.uk/id/eprint/369612
ISSN: 0006-4971
PURE UUID: 5405a926-ea53-4bf4-8c80-b26dacbc5f95

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Date deposited: 02 Oct 2014 10:28
Last modified: 17 Jul 2017 21:56

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Contributors

Author: Neil T. Young
Author: Edward C.P. Waller
Author: Rashmi Patel
Author: Ali Roghanian
Author: Jonathan M. Austyn
Author: John Trowsdale

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