Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes
| Autor: | Richard A. Flavell, Enric Esplugues, Jan Czyzyk, Raman Baldzizhar, Kevan C. Herold, Paula Preston-Hurlburt, Frans Gorus, Christine Fedorchuk, Kim Bottomly, Octavian Henegariu |
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| Přispěvatelé: | Pathologic Biochemistry and Physiology |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Adolescent Blotting Western Immunology Inflammation Mice SCID Nod Serpin Biology Transfection Autoantigens Article Serpins/immunology Mice Young Adult Autoantigens/immunology Mice Inbred NOD Internal medicine medicine Animals Humans Immunology and Allergy Child Serpins Tissue homeostasis Autoantibodies NOD mice Medicine(all) Mice Inbred BALB C Type 1 diabetes Autoantibody medicine.disease Mice Inbred C57BL Diabetes Mellitus Type 1 Endocrinology Diabetes Mellitus Type 1/immunology Child Preschool Humoral immunity medicine.symptom Autoantibodies/immunology |
| Zdroj: | The Journal of Immunology. 188:6319-6327 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Intracellular (clade B) OVA-serpin protease inhibitors play an important role in tissue homeostasis by protecting cells from death in response to hypo-osmotic stress, heat shock, and other stimuli. It is not known whether these serpins influence immunological tolerance and the risk for autoimmune diseases. We found that a fraction of young autoimmune diabetes-prone NOD mice had elevated levels of autoantibodies against a member of clade B family known as serpinB13. High levels of anti-serpinB13 Abs were accompanied by low levels of anti-insulin autoantibodies, reduced numbers of islet-associated T cells, and delayed onset of diabetes. Exposure to anti-serpinB13 mAb alone also decreased islet inflammation, and coadministration of this reagent and a suboptimal dose of anti-CD3 mAb accelerated recovery from diabetes. In a fashion similar to that discovered in the NOD model, a deficiency in humoral activity against serpinB13 was associated with early onset of human type 1 diabetes. These findings suggest that, in addition to limiting exposure to proteases within the cell, clade B serpins help to maintain homeostasis by inducing protective humoral immunity. |
| Databáze: | OpenAIRE |
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