Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease

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@article{13c721c7db3147ce918b33a67bd6a498,
title = "Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease",
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.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 healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sj{\"o}gren{\textquoteright}s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues.",
keywords = "14-3-3 Proteins, Adiponectin, Adult, Age Factors, Aged, Aging, Animals, Arthritis, Rheumatoid, Autoimmunity, B-Lymphocytes, Cadherins, Cell Adhesion, Cell Movement, Diabetes Mellitus, Type 1, Female, Gene Expression Regulation, Homeostasis, Human Umbilical Vein Endothelial Cells, Humans, Inflammation, Lysophospholipids, Male, Mice, Middle Aged, Peptides, Receptors, Adiponectin, Sphingosine, T-Lymphocytes, Young Adult, Chronic inflammation, autoimmune disease, trafficking, T cell",
author = "Ed Rainger and Myriam Chimen and Helen McGettrick and Sahithi Kuravi and Bonita Apta and Clara Yates and Amy Kennedy and A Odedra and Matthew Harrison and Ashley Martin and Francesca Barone and Saba Nayar and Jessica Hitchcock and Adam Cunningham and Karim Raza and Andrew Filer and DA Copland and A Dick and Joseph Robinson and Neena Kalia and Lucy Walker and Christopher Buckley and Gerard Nash and Partheepan Narendran and Mohammed Alassiri",
year = "2015",
month = may,
day = "15",
doi = "10.1038/nm.3842",
language = "English",
volume = "21",
pages = "467--475",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "5",

}

RIS

TY - JOUR

T1 - Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease

AU - Rainger, Ed

AU - Chimen, Myriam

AU - McGettrick, Helen

AU - Kuravi, Sahithi

AU - Apta, Bonita

AU - Yates, Clara

AU - Kennedy, Amy

AU - Odedra, A

AU - Harrison, Matthew

AU - Martin, Ashley

AU - Barone, Francesca

AU - Nayar, Saba

AU - Hitchcock, Jessica

AU - Cunningham, Adam

AU - Raza, Karim

AU - Filer, Andrew

AU - Copland, DA

AU - Dick, A

AU - Robinson, Joseph

AU - Kalia, Neena

AU - Walker, Lucy

AU - Buckley, Christopher

AU - Nash, Gerard

AU - Narendran, Partheepan

AU - Alassiri, Mohammed

PY - 2015/5/15

Y1 - 2015/5/15

N2 - 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.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 healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sjögren’s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues.

AB - 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.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 healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sjögren’s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues.

KW - 14-3-3 Proteins

KW - Adiponectin

KW - Adult

KW - Age Factors

KW - Aged

KW - Aging

KW - Animals

KW - Arthritis, Rheumatoid

KW - Autoimmunity

KW - B-Lymphocytes

KW - Cadherins

KW - Cell Adhesion

KW - Cell Movement

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Gene Expression Regulation

KW - Homeostasis

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Inflammation

KW - Lysophospholipids

KW - Male

KW - Mice

KW - Middle Aged

KW - Peptides

KW - Receptors, Adiponectin

KW - Sphingosine

KW - T-Lymphocytes

KW - Young Adult

KW - Chronic inflammation

KW - autoimmune disease

KW - trafficking

KW - T cell

U2 - 10.1038/nm.3842

DO - 10.1038/nm.3842

M3 - Article

C2 - 25894827

VL - 21

SP - 467

EP - 475

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 5

M1 - 3842

ER -