RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3-dependent control of STAT1
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RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3-dependent control of STAT1. / Pedersen, Esben Ditlev Kølle; Wang, Zhipeng; Stanley, Alanna; Peyrollier, Karine; Rösner, Lennart M; Werfel, Thomas; Quondamatteo, Fabio; Brakebusch, Cord Herbert.
I: Journal of Cell Science, Bind 125, Nr. Pt 22, 15.11.2012, s. 5379-90.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3-dependent control of STAT1
AU - Pedersen, Esben Ditlev Kølle
AU - Wang, Zhipeng
AU - Stanley, Alanna
AU - Peyrollier, Karine
AU - Rösner, Lennart M
AU - Werfel, Thomas
AU - Quondamatteo, Fabio
AU - Brakebusch, Cord Herbert
PY - 2012/11/15
Y1 - 2012/11/15
N2 - Crosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin, and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays an important role in modulating the interferon (IFN) response in skin. These RAC1 mutant mice showed increased sensitivity in an irritant contact dermatitis model, abnormal keratinocyte differentiation, and increased expression of immune response genes including the IFN signal transducer STAT1. Loss of RAC1 in keratinocytes decreased actin polymerization in vivo and in vitro and caused Arp2/3-dependent expression of STAT1, increased interferon sensitivity and upregulation of aberrant keratinocyte differentiation markers. This can be inhibited by the AP-1 inhibitor tanshinone IIA. Loss of RAC1 makes keratinocytes hypersensitive to inflammatory stimuli both in vitro and in vivo, suggesting a major role for RAC1 in regulating the crosstalk between the epidermis and the immune system.
AB - Crosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin, and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays an important role in modulating the interferon (IFN) response in skin. These RAC1 mutant mice showed increased sensitivity in an irritant contact dermatitis model, abnormal keratinocyte differentiation, and increased expression of immune response genes including the IFN signal transducer STAT1. Loss of RAC1 in keratinocytes decreased actin polymerization in vivo and in vitro and caused Arp2/3-dependent expression of STAT1, increased interferon sensitivity and upregulation of aberrant keratinocyte differentiation markers. This can be inhibited by the AP-1 inhibitor tanshinone IIA. Loss of RAC1 makes keratinocytes hypersensitive to inflammatory stimuli both in vitro and in vivo, suggesting a major role for RAC1 in regulating the crosstalk between the epidermis and the immune system.
KW - Actin Cytoskeleton
KW - Actin-Related Protein 2-3 Complex
KW - Actins
KW - Animals
KW - Cell Differentiation
KW - Diterpenes, Abietane
KW - Enzyme Activation
KW - Epidermis
KW - Gene Expression Regulation
KW - Inflammation
KW - Interferon-gamma
KW - Keratinocytes
KW - Leukocytes
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Neuropeptides
KW - Polymerization
KW - STAT1 Transcription Factor
KW - Signal Transduction
KW - Skin
KW - Tetradecanoylphorbol Acetate
KW - rac GTP-Binding Proteins
KW - rac1 GTP-Binding Protein
U2 - 10.1242/jcs.107011
DO - 10.1242/jcs.107011
M3 - Journal article
C2 - 22956547
VL - 125
SP - 5379
EP - 5390
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - Pt 22
ER -
ID: 108162875