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

Rossana Zaru, Stephen P. Matthews, Alexander J. Edgar, Alan R. Prescott, Diego Gomez-Nicola, André Hanauer, Colin Watts (Lead / Corresponding author)

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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.

Original languageEnglish
Pages (from-to)4264-4272
Number of pages9
JournalJournal of Immunology
Volume195
Issue number9
DOIs
Publication statusPublished - 1 Nov 2015

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Langerhans Cells
Cell Proliferation
Cell Count
Cell Size
1-Phosphatidylinositol 4-Kinase
Emigration and Immigration
Epidermis
Phosphotransferases
Ribosomal Protein S6 Kinases
Bone Marrow Cells

Cite this

Zaru, Rossana ; Matthews, Stephen P. ; Edgar, Alexander J. ; Prescott, Alan R. ; Gomez-Nicola, Diego ; Hanauer, André ; Watts, Colin. / The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning. In: Journal of Immunology. 2015 ; Vol. 195, No. 9. pp. 4264-4272.
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The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning. / Zaru, Rossana; Matthews, Stephen P.; Edgar, Alexander J.; Prescott, Alan R.; Gomez-Nicola, Diego; Hanauer, André; Watts, Colin (Lead / Corresponding author).

In: Journal of Immunology, Vol. 195, No. 9, 01.11.2015, p. 4264-4272.

Research output: Contribution to journalArticle

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