Exp Mol Med.  2016 Aug;48(8):e253. 10.1038/emm.2016.69.

Sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) reduces the migratory capacity of CCL21-treated monocyte-derived dendritic cells

• Hong CY
• Lee HJ
• Choi NR
• Jung SH
• Vo MC
• Hoang MD
• Kim HJ
• Lee JJ

• KMID: 2361540
• DOI: http://doi.org/10.1038/emm.2016.69

Abstract

The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca²âº ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins. In addition, CCL21 did not affect the mRNA levels of SERCA2 or its interacting protein Hax-1. Interestingly, SERCA2 expression was inversely related to DC migration in response to chemokine stimulation. The migratory capacity of CCL21-treated mDCs was decreased by the phospholipase C inhibitor U73122 and by the protein kinase C inhibitor BAPTA-AM. The migratory capacities of mDCs were increased in response to SERCA2 siRNA expression but were decreased by SERCA2 overexpression. In addition, DCs treated with a SERCA2-specific inhibitor (cyclopiazonic acid) had significantly increased migratory capacities as mDCs regardless of SERCA2 expression. Moreover, SERCA2 expression was dependent on DC maturation induced by cytokines or Toll-like receptor agonists. Therefore, the migratory capacities differed in differentially matured DCs. Taken together, these results suggest that SERCA2 contributes to the migration of CCL21-activated DCs as an important feature of the adaptive immune response and provide novel insights regarding the role of SERCA2 in DC functions.

MeSH Terms

Adaptive Immunity
Adenosine Triphosphatases*
Chemokine CCL21
Chemokines
Cytokines
Dendritic Cells*
Mitogen-Activated Protein Kinases
Protein Kinase C
Receptors, Chemokine
RNA, Messenger
RNA, Small Interfering
Sarcoplasmic Reticulum*
Toll-Like Receptors
Type C Phospholipases
Adenosine Triphosphatases
Chemokine CCL21
Chemokines
Cytokines
Mitogen-Activated Protein Kinases
Protein Kinase C
RNA, Messenger
RNA, Small Interfering
Receptors, Chemokine
Toll-Like Receptors
Type C Phospholipases