Sphingosine-1-phosphate/sphingosine-1-phosphate receptor 1 signaling is required for migration of naive human T cells from the thymus to the periphery
| Autor: | Rachel S. Resop, Marc Douaisi, Bianca Blom, Christel H. Uittenbogaart, Joshua Craft, Loes C. M. Jachimowski |
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| Přispěvatelé: | Other departments, Cell Biology and Histology, Experimental Immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CD3 T-Lymphocytes Immunology Population Gene Expression Thymus Gland Article Flow cytometry Immunophenotyping 03 medical and health sciences Cell Movement Sphingosine medicine Immunology and Allergy Humans education Receptor S1PR1 education.field_of_study Thymocytes medicine.diagnostic_test biology Chemotaxis organic chemicals Cell biology Thymocyte Receptors Lysosphingolipid 030104 developmental biology Phenotype KLF2 biology.protein lipids (amino acids peptides and proteins) Signal transduction Lysophospholipids Biomarkers Signal Transduction |
| Zdroj: | Journal of allergy and clinical immunology, 138(2), 551-557.e8. Mosby Inc. |
| ISSN: | 0091-6749 |
| Popis: | Background The mechanisms that govern the egress of mature thymocytes from the human thymus to the periphery remain understudied yet are of utmost importance to the field of basic immunology, as well as T-cell reconstitution in various immunodeficiencies. We examined the expression and function of sphingosine-1-phosphate (S1P) receptors in human thymocyte egress. Objectives We aimed to determine whether S1P receptors (S1P-Rs) play a role in mature human thymocyte egress and to identify the thymocyte population or populations that express S1P-Rs and respond to S1P by migrating across a concentration gradient. Methods Human thymocytes were exposed to S1P in Transwell plate migration assays coupled to flow cytometry to evaluate the response to S1P of thymocytes at different stages of maturation. Constitutive S1P-R expression was quantified by means of real-time PCR in sorted thymocyte subsets and flow cytometry. S1P-R1 and Kruppel-like factor 2 expression were monitored after S1P exposure by using flow cytometry and quantitative PCR. Results S1P-R1 was the prevalent S1P receptor on mature human thymocytes (CD3 hi CD27 + CD69 − ), the population that also demonstrated the greatest response to S1P in migration assays. Pretreatment with FTY720, an S1P-R1 nonselective modulator significantly reduced migration and suggested a role for S1P-R2 in retaining thymocytes in the tissue. Lastly, surface S1P-R1 expression, as well S1PR1 and Kruppel-like factor 2 (KLF2) transcripts, were significantly decreased in mature thymocytes on exposure to S1P. Conclusion Mature human thymocytes rely on S1P-R1 to migrate toward S1P. Taken in the context of murine work demonstrating that S1P is required for thymocyte egress to the periphery, our data highlight a new key chemokine for human thymocyte egress. |
| Databáze: | OpenAIRE |
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