一項(xiàng)可能幫助移植患者設(shè)計(jì)免疫抑制藥物的新研究發(fā)現(xiàn),，一個(gè)幫助新的免疫細(xì)胞從脾臟和淋巴結(jié)進(jìn)入身體的循環(huán)系統(tǒng)的強(qiáng)有力的信號(hào)發(fā)生分子有兩個(gè)不同的來(lái)源。統(tǒng)稱為淋巴細(xì)胞的免疫系統(tǒng)T細(xì)胞,、B細(xì)胞和自然殺傷細(xì)胞在胸腺、脾臟和淋巴結(jié)中發(fā)育后進(jìn)入血液和淋巴循環(huán),。一個(gè)叫S1P的分子幫助淋巴細(xì)胞進(jìn)入循環(huán),，是目前正在臨床試驗(yàn)的免疫抑制和自身免疫藥物的靶標(biāo)。Rajita Pappu和同事現(xiàn)在揭示,，幫助淋巴細(xì)胞進(jìn)入血液的S1P分子來(lái)自紅血細(xì)胞,，而幫助淋巴細(xì)胞進(jìn)入淋巴系統(tǒng)的S1P另有來(lái)源。這些供給使淋巴細(xì)胞跟隨一個(gè)淋巴組織和兩個(gè)循環(huán)系統(tǒng)之間的梯度,。該發(fā)現(xiàn)也許能幫助改進(jìn)免疫抑制和S1P路徑激活的方法,。
Published Online March 15, 2007
Science DOI: 10.1126/science.1139221
Science Express Index
Submitted on December 22, 2007
Accepted on March 2, 2007
Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate
Rajita Pappu 1, Susan R. Schwab 2, Ivo Cornelissen 1, João P. Pereira 2, Jean B. Regard 1, Ying Xu 2, Eric Camerer 1, Yao-Wu Zheng 1, Yong Huang 3, Jason G. Cyster 2*, Shaun R. Coughlin 1*
1 Cardiovascular Research Institute, University of California San Francisco, 600 16th Street S472D, San Francisco, CA 94143-2240, USA.
2 Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Ave., San Francisco, CA 94143-0414, USA.
3 Drug Studies Unit, Department of Biopharmaceutical Sciences, University of California San Francisco, 296 Lawrence Street, San Francisco, CA 94143-0446, USA.
* To whom correspondence should be addressed.
Jason G. Cyster , E-mail: [email protected]
Shaun R. Coughlin , E-mail: [email protected]
Lymphocytes require sphingosine-1-phosphate (S1P)-receptor-1 to exit lymphoid organs, but the source(s) of extracellular S1P and whether S1P directly promotes egress are unknown. Using mice in which the two kinases that generate S1P were conditionally ablated, we find that plasma S1P is mainly hematopoietic in origin with erythrocytes a major contributor, whereas lymph S1P is from a distinct radiation-resistant source. Lymphocyte egress from thymus and secondary lymphoid organs was markedly reduced in kinase-deficient mice. Restoration of S1P to plasma rescued egress to blood but not lymph, and the rescue required lymphocyte expression of S1P-receptor-1. Thus, separate sources provide S1P to plasma and lymph to help lymphocytes exit the low S1P environment of lymphoid organs. Disruption of compartmentalized S1P signaling is a plausible mechanism by which S1P-receptor-1 agonists function as immunosuppressives.
