Abstract
The immune system contains a series of checks and balances that maintain tolerance and prevent autoimmunity. Sialic acid-binding Ig-type lectins (Siglecs) are cell surface receptors found on immune cells and inhibit inflammation by recruiting protein tyrosine phosphatases to ITIMs. Islet-resident macrophages express Siglec-E, and Siglec-E expression decreases on islet-resident macrophages as insulitis progresses in the NOD mouse. The sialyltransferase ST8Sia6 generates α-2,8-disialic acids that are ligands for Siglec-E in vivo. We hypothesized that engaging Siglec-E through ST8Sia6-generated ligands may inhibit the development of immune-mediated diabetes. Constitutive overexpression of ST8Sia6 in pancreatic β cells mitigated hyperglycemia in the multiple low-dose streptozotocin model of diabetes, demonstrating that engagement of this immune receptor facilitates tolerance in the setting of inflammation and autoimmune disease.
Copyright © 2020 by The American Association of Immunologists, Inc.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation, B-Lymphocyte / immunology
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Antigens, Differentiation, B-Lymphocyte / metabolism
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Autoimmunity / immunology
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Diabetes Mellitus / chemically induced*
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Diabetes Mellitus / immunology
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Diabetes Mellitus / metabolism*
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / immunology
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Diabetes Mellitus, Experimental / metabolism
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Disease Models, Animal
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Female
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Humans
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Hyperglycemia / immunology
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Hyperglycemia / metabolism
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Immune Tolerance / immunology
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Inflammation / immunology
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Inflammation / metabolism
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Insulin-Secreting Cells / immunology
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Insulin-Secreting Cells / metabolism
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Ligands
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Macrophages / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Sialic Acid Binding Ig-like Lectin 2 / immunology
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Sialic Acid Binding Ig-like Lectin 2 / metabolism
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Sialyltransferases / immunology
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Sialyltransferases / metabolism*
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Streptozocin / pharmacology*
Substances
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Antigens, Differentiation, B-Lymphocyte
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Ligands
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Receptors, Immunologic
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Sialic Acid Binding Ig-like Lectin 2
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Streptozocin
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Sialyltransferases