The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling

Victoria Zyulina; Koon Kiu Yan; Bensheng Ju; Elke Schwarzenberger; Christina Passegger; Carmen Tam-Amersdorfer; Qingfei Pan; Tommaso Sconocchia; Christian Pollack; Bridget Shaner; Armin Zebisch; John Easton; Jiyang Yu; Jose M. Silva; Herbert Strobl

doi:10.1016/j.celrep.2021.109049

The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling

Victoria Zyulina, Koon Kiu Yan, Bensheng Ju, Elke Schwarzenberger, Christina Passegger, Carmen Tam-Amersdorfer, Qingfei Pan, Tommaso Sconocchia, Christian Pollack, Bridget Shaner, Armin Zebisch, John Easton, Jiyang Yu, Jose M. Silva, Herbert Strobl

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7 Scopus citations

Abstract

Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened LCs versus moDCs for differentially expressed microRNAs (miRNAs). This revealed that miR-424/503 is the most strongly inversely regulated (moDCs > LCs). We here demonstrate that miR-424/503 is induced during moDC differentiation and promotes moDC differentiation in human and mouse. Inversely, forced repression of miR-424 during moDC differentiation facilitates TGF-β1-dependent LC differentiation. Mechanistically, miR-424/503 deficiency in monocyte/DC precursors leads to the induction of TGF-β1 response genes critical for LC differentiation. Therefore, the miR-424/503 gene cluster plays a decisive role in anti-inflammatory LC versus pro-inflammatory moDC differentiation from monocytes.

Original language	English
Article number	109049
Journal	Cell Reports
Volume	35
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2021.109049
State	Published - 27 Apr 2021

Keywords

IL-4
Langerhans cell differentiation
TGF-β1 signaling
lineage decision
miR-424
microRNA 424(322)/503 gene cluster
monocyte-derived DC

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10.1016/j.celrep.2021.109049

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Zyulina, V., Yan, K. K., Ju, B., Schwarzenberger, E., Passegger, C., Tam-Amersdorfer, C., Pan, Q., Sconocchia, T., Pollack, C., Shaner, B., Zebisch, A., Easton, J., Yu, J., Silva, J. M., & Strobl, H. (2021). The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling. Cell Reports, 35(4), Article 109049. https://doi.org/10.1016/j.celrep.2021.109049

@article{13773bfaa435472cac923d0d5b8193b3,

title = "The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling",

abstract = "Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened LCs versus moDCs for differentially expressed microRNAs (miRNAs). This revealed that miR-424/503 is the most strongly inversely regulated (moDCs > LCs). We here demonstrate that miR-424/503 is induced during moDC differentiation and promotes moDC differentiation in human and mouse. Inversely, forced repression of miR-424 during moDC differentiation facilitates TGF-β1-dependent LC differentiation. Mechanistically, miR-424/503 deficiency in monocyte/DC precursors leads to the induction of TGF-β1 response genes critical for LC differentiation. Therefore, the miR-424/503 gene cluster plays a decisive role in anti-inflammatory LC versus pro-inflammatory moDC differentiation from monocytes.",

keywords = "IL-4, Langerhans cell differentiation, TGF-β1 signaling, lineage decision, miR-424, microRNA 424(322)/503 gene cluster, monocyte-derived DC",

author = "Victoria Zyulina and Yan, {Koon Kiu} and Bensheng Ju and Elke Schwarzenberger and Christina Passegger and Carmen Tam-Amersdorfer and Qingfei Pan and Tommaso Sconocchia and Christian Pollack and Bridget Shaner and Armin Zebisch and John Easton and Jiyang Yu and Silva, {Jose M.} and Herbert Strobl",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = apr,

day = "27",

doi = "10.1016/j.celrep.2021.109049",

language = "English",

volume = "35",

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Zyulina, V, Yan, KK, Ju, B, Schwarzenberger, E, Passegger, C, Tam-Amersdorfer, C, Pan, Q, Sconocchia, T, Pollack, C, Shaner, B, Zebisch, A, Easton, J, Yu, J, Silva, JM & Strobl, H 2021, 'The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling', Cell Reports, vol. 35, no. 4, 109049. https://doi.org/10.1016/j.celrep.2021.109049

TY - JOUR

T1 - The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling

AU - Zyulina, Victoria

AU - Yan, Koon Kiu

AU - Ju, Bensheng

AU - Schwarzenberger, Elke

AU - Passegger, Christina

AU - Tam-Amersdorfer, Carmen

AU - Pan, Qingfei

AU - Sconocchia, Tommaso

AU - Pollack, Christian

AU - Shaner, Bridget

AU - Zebisch, Armin

AU - Easton, John

AU - Yu, Jiyang

AU - Silva, Jose M.

AU - Strobl, Herbert

PY - 2021/4/27

Y1 - 2021/4/27

N2 - Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened LCs versus moDCs for differentially expressed microRNAs (miRNAs). This revealed that miR-424/503 is the most strongly inversely regulated (moDCs > LCs). We here demonstrate that miR-424/503 is induced during moDC differentiation and promotes moDC differentiation in human and mouse. Inversely, forced repression of miR-424 during moDC differentiation facilitates TGF-β1-dependent LC differentiation. Mechanistically, miR-424/503 deficiency in monocyte/DC precursors leads to the induction of TGF-β1 response genes critical for LC differentiation. Therefore, the miR-424/503 gene cluster plays a decisive role in anti-inflammatory LC versus pro-inflammatory moDC differentiation from monocytes.

AB - Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened LCs versus moDCs for differentially expressed microRNAs (miRNAs). This revealed that miR-424/503 is the most strongly inversely regulated (moDCs > LCs). We here demonstrate that miR-424/503 is induced during moDC differentiation and promotes moDC differentiation in human and mouse. Inversely, forced repression of miR-424 during moDC differentiation facilitates TGF-β1-dependent LC differentiation. Mechanistically, miR-424/503 deficiency in monocyte/DC precursors leads to the induction of TGF-β1 response genes critical for LC differentiation. Therefore, the miR-424/503 gene cluster plays a decisive role in anti-inflammatory LC versus pro-inflammatory moDC differentiation from monocytes.

KW - IL-4

KW - Langerhans cell differentiation

KW - TGF-β1 signaling

KW - lineage decision

KW - miR-424

KW - microRNA 424(322)/503 gene cluster

KW - monocyte-derived DC

UR - http://www.scopus.com/inward/record.url?scp=85105052026&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109049

DO - 10.1016/j.celrep.2021.109049

M3 - Article

C2 - 33910004

AN - SCOPUS:85105052026

SN - 2211-1247

VL - 35

JO - Cell Reports

JF - Cell Reports

IS - 4

M1 - 109049

ER -

The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling

Abstract

Keywords

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