TY  - JOUR
A1  - Sic, Heiko
A1  - Kraus, Helene
A1  - Madl, Josef
A1  - Flittner, Karl-Andreas
A1  - von Muenchow, Audrey Lilly
A1  - Pieper, Kathrin
A1  - Rizzi, Marta
A1  - Kienzler, Anne-Kathrin
A1  - Ayata, Korcan
A1  - Rauer, Sebastian
A1  - Kleuser, Burkhard
A1  - Salzer, Ulrich
A1  - Burger, Meike
A1  - Zirlik, Katja
A1  - Lougaris, Vassilios
A1  - Plebani, Alessandro
A1  - Roemer, Winfried
A1  - Loeffler, Christoph
A1  - Scaramuzza, Samantha
A1  - Villa, Anna
A1  - Noguchi, Emiko
A1  - Grimbacher, Bodo
A1  - Eibel, Hermann
T1  - Sphingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis
JF  - The journal of allergy and clinical immunology
N2  - Background: Five different G protein-coupled sphingosine-1-phosphate (S1P) receptors (S1P1-S1P5) regulate a variety of physiologic and pathophysiologic processes, including lymphocyte circulation, multiple sclerosis (MS), and cancer. Although B-lymphocyte circulation plays an important role in these processes and is essential for normal immune responses, little is known about S1P receptors in human B cells.
 Objective: To explore their function and signaling, we studied B-cell lines and primary B cells from control subjects, patients with leukemia, patients with S1P receptor inhibitor-treated MS, and patients with primary immunodeficiencies.
 Methods: S1P receptor expression was analyzed by using multicolor immunofluorescence microscopy and quantitative PCR. Transwell assays were used to study cell migration. S1P receptor internalization was visualized by means of time-lapse imaging with fluorescent S1P receptor fusion proteins expressed by using lentiviral gene transfer. B-lymphocyte subsets were characterized by means of flow cytometry and immunofluorescence microscopy.
 Results: Showing that different B-cell populations express different combinations of S1P receptors, we found that S1P1 promotes migration, whereas S1P4 modulates and S1P2 inhibits S1P1 signals. Expression of CD69 in activated B lymphocytes and B cells from patients with chronic lymphocytic leukemia inhibited S1P-induced migration. Studying B-cell lines, normal B lymphocytes, and B cells from patients with primary immunodeficiencies, we identified Bruton tyrosine kinase, beta-arrestin 2, LPS-responsive beige-like anchor protein, dedicator of cytokinesis 8, and Wiskott-Aldrich syndrome protein as critical signaling components downstream of S1P1.
 Conclusion: Thus S1P receptor signaling regulates human B-cell circulation and might be a factor contributing to the pathology of MS, chronic lymphocytic leukemia, and primary immunodeficiencies.
KW  - Sphingosine-1-phosphate
KW  - B cells
KW  - migration
KW  - autoimmunity
KW  - circulation
KW  - fingolimod
KW  - FTY720
KW  - primary immunodeficiencies
Y1  - 2014
U6  - https://doi.org/10.1016/j.jaci.2014.01.037
SN  - 0091-6749
SN  - 1097-6825
VL  - 134
IS  - 2
SP  - 420
EP  - +
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Arlt, Olga
A1  - Schwiebs, Anja
A1  - Japtok, Lukasz
A1  - Rueger, Katja
A1  - Katzy, Elisabeth
A1  - Kleuser, Burkhard
A1  - Radeke, Heinfried H.
T1  - Sphingosine-1-Phosphate modulates dendritic cell function: focus on non-migratory effects in vitro and in vivo
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen presenting cells are the capture, endosomal processing and presentation of antigens, providing them an exclusive ability to provoke adaptive immune responses and to induce and control tolerance. Immature DCs capture and process antigens, migrate towards secondary lymphoid organs where they present antigens to naive T cells in a well synchronized sequence of procedures referred to as maturation. Indeed, recent research indicated that sphingolipids are modulators of essential steps in DC homeostasis. It has been recognized that sphingolipids not only modulate the development of DC subtypes from precursor cells but also influence functional activities of DCs such as antigen capture, and cytokine profiling. Thus, it is not astonishing that sphingolipids and sphingolipid metabolism play a substantial role in inflammatory diseases that are modulated by DCs. Here we highlight the function of sphingosine 1-phosphate (S1P) on DC homeostasis and the role of SIP and SW metabolism in inflammatory diseases.
KW  - Sphingosine-1-phosphate
KW  - Dendritic cells
KW  - Fingolimod
KW  - IL-12
KW  - Inflammation
Y1  - 2014
U6  - https://doi.org/10.1159/000362982
SN  - 1015-8987
SN  - 1421-9778
VL  - 34
IS  - 1
SP  - 27
EP  - 44
PB  - Karger
CY  - Basel
ER  -