Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease
| Autor: | Sahithi J. Kuravi, Mohammed Alassiri, Francesca Barone, Saba Nayar, Joseph Robinson, Christopher D. Buckley, Parth Narendran, Helen M. McGettrick, Lucy S. K. Walker, David A. Copland, Jessica Hitchcock, Karim Raza, Bonita H. R. Apta, Arjun Odedra, Andrew Filer, Amy Kennedy, Clara M. Yates, Andrew D. Dick, Myriam Chimen, Ashley Martin, Gerard B. Nash, G. Ed Rainger, Neena Kalia, Matthew J. Harrison, Adam F. Cunningham |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Aging T cell Lymphocyte T-Lymphocytes Inflammation Autoimmunity Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Pathogenesis Arthritis Rheumatoid Mice Young Adult Cell Movement Sphingosine medicine Cell Adhesion Human Umbilical Vein Endothelial Cells Animals Homeostasis Humans Secretion Receptor B cell Aged B-Lymphocytes Age Factors General Medicine Middle Aged Cadherins 3. Good health medicine.anatomical_structure Diabetes Mellitus Type 1 14-3-3 Proteins Gene Expression Regulation Immunology Female Adiponectin medicine.symptom Lysophospholipids Receptors Adiponectin Peptides |
| Zdroj: | Nature medicine. 21(5) |
| ISSN: | 1546-170X |
| Popis: | During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjogren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues. |
| Databáze: | OpenAIRE |
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