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The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning

The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning
The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning
Langerhans cells (LC), the dendritic cells of the epidermis, are distributed in a distinctive regularly spaced array. In the mouse, the LC array is established in the first few days of life from proliferating local precursors, but the regulating signaling pathways are not fully understood. We found that mice lacking the kinase phosphoinositide-dependent kinase 1 selectively lack LC. Deletion of the phosphoinositide-dependent kinase 1 target kinases, ribosomal S6 kinase 1 (Rsk1) and Rsk2, produced a striking perturbation in the LC network: LC density was reduced 2-fold, but LC size was increased by the same magnitude. Reduced LC numbers in Rsk1/2?/? mice was not due to accelerated emigration from the skin but rather to reduced proliferation at least in adults. Rsk1/2 were required for normal LC patterning in neonates, but not when LC were ablated in adults and replaced by bone marrow–derived cells. Increased LC size was an intrinsic response to reduced LC numbers, reversible on LC emigration, and could be observed in wild type epidermis where LC size also correlated inversely with LC density. Our results identify a key signaling pathway needed to establish a normal LC network and suggest that LC might maintain epidermal surveillance by increasing their “footprint” when their numbers are limited
0022-1767
1-10
Zaru, R.
6029a600-27f9-42c0-ae68-d1d92a6d8ad0
Matthews, S.P.
c720dd73-03be-4657-9202-c264304dc24d
Edgar, A.J.
221ac7c7-8fc3-4dd4-a8e3-1062a9fc9fc9
Prescott, A.R.
8be196d0-ff21-42b3-8bce-b116260143f6
Gomez-Nicola, D.
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Hanauer, A.
36729b03-ef95-47aa-b973-8e977f5b7218
Watts, C.
e02080c6-ce2c-4dfe-892d-b4f270538d24
Zaru, R.
6029a600-27f9-42c0-ae68-d1d92a6d8ad0
Matthews, S.P.
c720dd73-03be-4657-9202-c264304dc24d
Edgar, A.J.
221ac7c7-8fc3-4dd4-a8e3-1062a9fc9fc9
Prescott, A.R.
8be196d0-ff21-42b3-8bce-b116260143f6
Gomez-Nicola, D.
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Hanauer, A.
36729b03-ef95-47aa-b973-8e977f5b7218
Watts, C.
e02080c6-ce2c-4dfe-892d-b4f270538d24

Zaru, R., Matthews, S.P., Edgar, A.J., Prescott, A.R., Gomez-Nicola, D., Hanauer, A. and Watts, C. (2015) The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning. Journal of Immunology, 1-10. (doi:10.4049/?jimmunol.1501520). (PMID:26401001)

Record type: Article

Abstract

Langerhans cells (LC), the dendritic cells of the epidermis, are distributed in a distinctive regularly spaced array. In the mouse, the LC array is established in the first few days of life from proliferating local precursors, but the regulating signaling pathways are not fully understood. We found that mice lacking the kinase phosphoinositide-dependent kinase 1 selectively lack LC. Deletion of the phosphoinositide-dependent kinase 1 target kinases, ribosomal S6 kinase 1 (Rsk1) and Rsk2, produced a striking perturbation in the LC network: LC density was reduced 2-fold, but LC size was increased by the same magnitude. Reduced LC numbers in Rsk1/2?/? mice was not due to accelerated emigration from the skin but rather to reduced proliferation at least in adults. Rsk1/2 were required for normal LC patterning in neonates, but not when LC were ablated in adults and replaced by bone marrow–derived cells. Increased LC size was an intrinsic response to reduced LC numbers, reversible on LC emigration, and could be observed in wild type epidermis where LC size also correlated inversely with LC density. Our results identify a key signaling pathway needed to establish a normal LC network and suggest that LC might maintain epidermal surveillance by increasing their “footprint” when their numbers are limited

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Accepted/In Press date: 26 August 2015
Published date: 23 September 2015
Organisations: Biomedicine

Identifiers

Local EPrints ID: 381995
URI: https://eprints.soton.ac.uk/id/eprint/381995
ISSN: 0022-1767
PURE UUID: ec7b0ce8-80fa-4419-a047-a76468ba38e7
ORCID for D. Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

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Date deposited: 16 Oct 2015 15:14
Last modified: 06 Jun 2018 12:33

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