Abstract
Dendritic cells (DCs) need to migrate in the interstitial environment of peripheral tissues to reach secondary lymphoid organs and initiate a suitable immune response. Whether and how inflamed tissues instruct DCs to emigrate is not fully understood. In this study, we report the unexpected finding that the epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human DCs in a cell-autonomous manner. TSLP induced the polarization of both microtubule and actin cytoskeletons and promoted DC 3-dimensional migration in transwell as well as in microfabricated channels that mimic the confined environment of peripheral tissues. TSLP-induced migration relied on the actin-based motor myosin II and was inhibited by blebbistatin. Accordingly, TSLP triggered the redistribution of phosphorylated myosin II regulatory light chain to the actin cortex, indicating that TSLP induces DC migration by promoting actomyosin contractility. Thus, TSLP produced by epithelial cells in inflamed tissue has a critical function in licensing DCs for cell-autonomous migration. This indicates that cytokines can directly trigger cell migration, which has important implications in immune physiopathology and vaccine design.
| Original language | English |
|---|---|
| Pages (from-to) | 3862-3869 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 118 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Oct 6 2011 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in confined environments. / Fernandez, Maria Isabel; Heuzé, Mélina L.; Martinez-Cingolani, Carolina; Volpe, Elisabetta; Donnadieu, Marie Helene; Piel, Matthieu; Homey, Bernhard; Lennon-Duménil, Ana Maria; Soumelis, Vassili.
In: Blood, Vol. 118, No. 14, 06.10.2011, p. 3862-3869.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in confined environments
AU - Fernandez, Maria Isabel
AU - Heuzé, Mélina L.
AU - Martinez-Cingolani, Carolina
AU - Volpe, Elisabetta
AU - Donnadieu, Marie Helene
AU - Piel, Matthieu
AU - Homey, Bernhard
AU - Lennon-Duménil, Ana Maria
AU - Soumelis, Vassili
PY - 2011/10/6
Y1 - 2011/10/6
N2 - Dendritic cells (DCs) need to migrate in the interstitial environment of peripheral tissues to reach secondary lymphoid organs and initiate a suitable immune response. Whether and how inflamed tissues instruct DCs to emigrate is not fully understood. In this study, we report the unexpected finding that the epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human DCs in a cell-autonomous manner. TSLP induced the polarization of both microtubule and actin cytoskeletons and promoted DC 3-dimensional migration in transwell as well as in microfabricated channels that mimic the confined environment of peripheral tissues. TSLP-induced migration relied on the actin-based motor myosin II and was inhibited by blebbistatin. Accordingly, TSLP triggered the redistribution of phosphorylated myosin II regulatory light chain to the actin cortex, indicating that TSLP induces DC migration by promoting actomyosin contractility. Thus, TSLP produced by epithelial cells in inflamed tissue has a critical function in licensing DCs for cell-autonomous migration. This indicates that cytokines can directly trigger cell migration, which has important implications in immune physiopathology and vaccine design.
AB - Dendritic cells (DCs) need to migrate in the interstitial environment of peripheral tissues to reach secondary lymphoid organs and initiate a suitable immune response. Whether and how inflamed tissues instruct DCs to emigrate is not fully understood. In this study, we report the unexpected finding that the epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human DCs in a cell-autonomous manner. TSLP induced the polarization of both microtubule and actin cytoskeletons and promoted DC 3-dimensional migration in transwell as well as in microfabricated channels that mimic the confined environment of peripheral tissues. TSLP-induced migration relied on the actin-based motor myosin II and was inhibited by blebbistatin. Accordingly, TSLP triggered the redistribution of phosphorylated myosin II regulatory light chain to the actin cortex, indicating that TSLP induces DC migration by promoting actomyosin contractility. Thus, TSLP produced by epithelial cells in inflamed tissue has a critical function in licensing DCs for cell-autonomous migration. This indicates that cytokines can directly trigger cell migration, which has important implications in immune physiopathology and vaccine design.
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U2 - 10.1182/blood-2010-12-323089
DO - 10.1182/blood-2010-12-323089
M3 - Article
C2 - 21772055
AN - SCOPUS:80053620974
VL - 118
SP - 3862
EP - 3869
JO - Blood
JF - Blood
SN - 0006-4971
IS - 14
ER -