Langerhans cell homeostasis in mice is dependent on mTORC1 but not mTORC2 function.

Abstract:

:The PI3K/Akt/mTOR pathway has emerged as a critical regulator of dendritic cell (DC) development and function. The kinase mTOR is found in 2 distinct complexes, mTORC1 and mTORC2. In this study, we show that mTORC1 but not mTORC2 is required for epidermal Langerhans cell (LC) homeostasis. Although the initial seeding of the epidermis with LCs is not affected, the lack of mTORC1 activity in DCs by conditional deletion of Raptor leads to a progressive loss of LCs in the skin of mice. Ablation of mTORC2 function by deletion of Rictor results in a modest reduction of LCs in skin draining lymph nodes. In young mice Raptor-deficient LCs show an increased tendency to leave the skin, leading to a higher frequency of migratory DCs in skin draining lymph nodes, indicating that the loss of LCs results from enhanced migration. LCs lacking Raptor are smaller and display reduced expression of Langerin, E-cadherin, β-catenin, and CCR7 but unchanged levels of MHC-II, ruling out enhanced spontaneous maturation. Ki-67 and annexin V stainings revealed a faster turnover rate and increased apoptosis of Raptor-deficient LCs, which might additionally affect the preservation of the LC network. Taken together our results show that the homeostasis of LCs strictly depends on mTORC1.

journal_name

Blood

journal_title

Blood

authors

Kellersch B,Brocker T

doi

10.1182/blood-2012-06-439786

subject

Has Abstract

pub_date

2013-01-10 00:00:00

pages

298-307

issue

2

eissn

0006-4971

issn

1528-0020

pii

blood-2012-06-439786

journal_volume

121

pub_type

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