Title |
Homeostatic regulation of T cell trafficking by a B cell–derived peptide is impaired in autoimmune and chronic inflammatory disease
|
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Published in |
Nature Medicine, April 2015
|
DOI | 10.1038/nm.3842 |
Pubmed ID | |
Authors |
Myriam Chimen, Helen M McGettrick, Bonita Apta, Sahithi J Kuravi, Clara M Yates, Amy Kennedy, Arjun Odedra, Mohammed Alassiri, Matthew Harrison, Ashley Martin, Francesca Barone, Saba Nayar, Jessica R Hitchcock, Adam F Cunningham, Karim Raza, Andrew Filer, David A Copland, Andrew D Dick, Joseph Robinson, Neena Kalia, Lucy S K Walker, Christopher D Buckley, Gerard B Nash, Parth Narendran, G Ed Rainger |
Abstract |
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 Sjögren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 19% |
Spain | 4 | 13% |
Canada | 2 | 6% |
Russia | 1 | 3% |
Sweden | 1 | 3% |
New Zealand | 1 | 3% |
Saudi Arabia | 1 | 3% |
Unknown | 16 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 19 | 59% |
Scientists | 8 | 25% |
Science communicators (journalists, bloggers, editors) | 3 | 9% |
Practitioners (doctors, other healthcare professionals) | 2 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 2 | <1% |
Turkey | 1 | <1% |
Brazil | 1 | <1% |
United Kingdom | 1 | <1% |
United States | 1 | <1% |
Unknown | 215 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 49 | 22% |
Researcher | 49 | 22% |
Student > Bachelor | 22 | 10% |
Student > Master | 21 | 10% |
Other | 13 | 6% |
Other | 41 | 19% |
Unknown | 26 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 61 | 28% |
Medicine and Dentistry | 47 | 21% |
Immunology and Microbiology | 37 | 17% |
Biochemistry, Genetics and Molecular Biology | 25 | 11% |
Engineering | 3 | 1% |
Other | 15 | 7% |
Unknown | 33 | 15% |