Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease

被引:86
|
作者
Karuppuchamy, T. [1 ,2 ]
Behrens, E-H [1 ,2 ]
Gonzalez-Cabrera, P. [3 ]
Sarkisyan, G. [3 ]
Gima, L. [1 ,2 ]
Boyer, J. D. [1 ,2 ]
Bamias, G. [4 ]
Jedlicka, P. [5 ]
Veny, M. [1 ,2 ]
Clark, D. [1 ,2 ]
Peach, R. [6 ]
Scott, F. [6 ]
Rosen, H. [3 ]
Rivera-Nieves, J. [1 ,2 ]
机构
[1] Univ Calif San Diego, Ctr Inflammatory Bowel Dis, Div Gastroenterol, La Jolla, CA 92093 USA
[2] VA San Diego Healthcare Syst, San Diego, CA 92161 USA
[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[4] Laikon Gen Hosp, Acad Dept Gastroenterol, Athens, Greece
[5] Univ Colorado Hlth Sci, Dept Pathol, Aurora, CO USA
[6] Receptos Inc, La Jolla, CA USA
基金
美国国家卫生研究院;
关键词
SPHINGOSINE 1-PHOSPHATE RECEPTOR; GENE-DEFICIENT MICE; CROHNS-DISEASE; MURINE ILEITIS; T-CELLS; MAINTENANCE THERAPY; MULTIPLE-SCLEROSIS; ULCERATIVE-COLITIS; FTY720; MIGRATION;
D O I
10.1038/mi.2016.35
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The sphingosine-1-phosphate receptor-1 (S1P(1)) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P(1) in intestine using S1P(1)-eGFP mice, the regulation of S1P(1) expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4(+) CD45RB(hi) cells, and by crossing a mouse with TNF-driven ileitis with S1P(1)-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P(1) expression. We found that not only T and B cells express S1P(1), but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P(1) expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P(1) degradation and retention of Naive but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P(1) expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.
引用
收藏
页码:162 / 171
页数:10
相关论文
共 50 条
  • [41] Sphingosine-1-phosphate (S1P) in ovarian physiology and disease
    Hernandez-Coronado, Cyndi G.
    Guzman, Adrian
    Castillo-Juarez, Hector
    Zamora-Gutierrez, Diana
    Maria Rosales-Torres, Ana
    ANNALES D ENDOCRINOLOGIE, 2019, 80 (5-6) : 263 - 272
  • [43] SPHINGOSINE-1-PHOSPHATE RECEPTORS S1P1 AND S1P3 REGULATE THE TRANSENDOTHELIAL TRANSPORT OF HDL AND LDL ANTAGONISTICALLY
    Velagapudi, Srividya
    Yalcinkaya, Mustafa
    Rohrer, Lucia
    von Eckardstein, Arnold
    ATHEROSCLEROSIS SUPPLEMENTS, 2018, 32 : 125 - 125
  • [44] Aryl Ether-Derived Sphingosine-1-Phosphate Receptor (S1P1) Modulators: Optimization of the PK, PD, and Safety Profiles
    Xiao, Zili
    Yang, Michael G.
    Dhar, T. G. Murali
    Xiao, Hai-Yun
    Gilmore, John L.
    Marcoux, David
    McIntyre, Kim W.
    Taylor, Tracy L.
    Shi, Hong
    Levesque, Paul C.
    Marino, Anthony M.
    Cornelius, Georgia
    Mathur, Arvind
    Shen, Ding Ren
    Cvijic, Mary Ellen
    Lehman-McKeeman, Lois D.
    Sun, Huadong
    Xie, Jenny H.
    Carter, Percy H.
    Dyckman, Alaric J.
    ACS MEDICINAL CHEMISTRY LETTERS, 2020, 11 (09): : 1766 - 1772
  • [45] Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease
    Wang, Xuewen
    Chen, Shuhua
    Xiang, Hong
    Liang, Ziwei
    Lu, Hongwei
    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2021, 25 (06) : 2740 - 2749
  • [46] A Novel Sphingosine-1-Phosphate Receptor 1 Antagonist Prevents the Proliferation and Relaxation of Vascular Endothelial Cells by Sphingosine-1-Phosphate
    Yonesu, Kiyoaki
    Nakamura, Tsuyoshi
    Mizuno, Yumiko
    Suzuki, Chie
    Nagayama, Takahiro
    Satoh, Susumu
    Nara, Futoshi
    BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2010, 33 (09) : 1500 - 1505
  • [47] Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease
    Wollny, Tomasz
    Watek, Marzena
    Durnas, Bonita
    Niemirowicz, Katarzyna
    Piktel, Ewelina
    Zendzian-Piotrowska, Malgorzata
    Gozdz, Stanislaw
    Bucki, Robert
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (04)
  • [48] EFFECT OF CENERIMOD, A SPHINGOSINE-1-PHOSPHATE RECEPTOR 1 (S1P1) MODULATOR, ON THE FORMATION OF TERTIARY LYMPHOID STRUCTURES IN A MOUSE MODEL OF SJOGREN'S SYNDROME
    Nayar, S.
    Campos, J.
    Smith, C.
    Buckley, C. D.
    Froidevaux, S.
    Wartha, K.
    Seemayer, C.
    Barone, F.
    ANNALS OF THE RHEUMATIC DISEASES, 2018, 77 : A65 - A65
  • [49] Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration
    Allende, ML
    Dreier, JL
    Mandala, S
    Proia, RL
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) : 15396 - 15401
  • [50] Inflammation Modulates the Sphingosine-1-Phosphate Pathway in Inflammatory Bowel Disease (IBD)
    Karuppuchamy, Thangaraj
    Behrens, En-hui
    Gonzalez-Cabrera, Pedro
    Sarkisyan, Gor
    Gima, Lauren
    Boyer, Joshua
    Bamias, Giorgos
    Jedlicka, Paul
    Veny, Marisol
    Clark, David
    Peach, Robert
    Scott, Fiona
    Rosen, Hugh
    Rivera-Nieves, Jesus
    GASTROENTEROLOGY, 2016, 150 (04) : S195 - S195