Correction for Bandala-Sanchez et al., CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function
| Autor: | Andrea Maggioni, Peter Czabotar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
HMGB1
Male sialoglycan Multidisciplinary Siglec-10 Protein Tyrosine Phosphatase Non-Receptor Type 6 T-Lymphocytes Amino Acid Motifs Receptors Antigen T-Cell T cell chemical and pharmacologic phenomena Biological Sciences Corrections Antibodies Immunology and Inflammation CD52 Antigen Protein Domains Lectins CD52 Humans Female HMGB1 Protein |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| Popis: | Significance Inflammation is a protective response of the body’s immune system against harmful stimuli such as pathogenic microorganisms, toxins, or damaged cells. However, if excessive or prolonged, inflammation may be harmful and therefore has to be regulated. Soluble CD52 is a natural sialoglycopeptide and immune regulator that suppresses inflammatory responses. We elucidated the mechanism of this effect by showing that soluble CD52 first sequesters a mediator of inflammation called HMGB1; in turn, this promotes binding of the sialylated CD52 glycan to an inhibitory receptor, sialic acid-binding immunoglobulin-like lectin (Siglec)-10, present on activated T cells and other immune cells. This concerted antiinflammatory mechanism driven by soluble CD52 may contribute to immune-inflammatory homeostasis and underscores the therapeutic potential of soluble CD52. CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function. We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1). CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10. Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1. CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR). Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR. This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|