Dendritic cell immunoreceptor: A novel receptor for intravenous immunoglobulin mediates induction of regulatory T cells
Section snippets
Fractionation of IVIg
Fractionation of IVIg was performed by using Sambucus nigra agglutinin–lectin affinity columns, according to the manufacturer’s protocol. IVIg (Talecris Biotherapeutics, Mississauga, Ontario, Canada) was loaded onto a 2-mL Sambucus nigra agglutinin column. The flow-through fraction (sialic acid–depleted intravenous immunoglobulin [non-SA-IVIg]) was collected by washing the column with 10 mL of Tris-buffered saline. The SA-IVIg fraction was eluted by using 4 mL of 0.5 mol/L lactose. The
Sialylated IgG is required for the anti-inflammatory effect of IVIg
IVIg, SA-IVIg, or non-SA-IVIg were administered to OVA-sensitized mice 1 day before allergen challenge to address whether sialylated IgG attenuates allergic airways disease (AAD). SA-IVIg attenuated MCh-induced AHR in OVA-challenged mice comparable with intact IVIg (Fig 1, A) at a 10-fold lower dose. Inhibition of AHR by IVIg and SA-IVIg was accompanied by a significant increase in the frequency of Treg cells within the lungs (Fig 1, B and C). Administration of non-SA-IVIg did not prevent
Discussion
IgG is a crucial effector molecule in host defense recognized for its role in pathogen elimination and autoimmune diseases. However, there are many examples of IgG contributing to immune tolerance, and IVIg is frequently used as disease-modifying therapy for autoimmune and inflammatory conditions.17 Using a murine model of AAD, we reported that high-dose IVIg induces Foxp3+ Treg cells from Foxp3−CD4+ T cells, attenuating allergen-induced AHR. The effect of IVIg is the result of functional
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2023, Journal of Allergy and Clinical Immunology: In PracticeSialylated IVIg binding to DC-SIGN<sup>+</sup> Hofbauer cells induces immune tolerance through the caveolin-1/NF-kB pathway and IL-10 secretion
2023, Clinical ImmunologyCitation Excerpt :In a mechanical analysis of the roles of IVIg, Ravetch et al. revealed that the anti-inflammatory activity of IVIg is mediated mainly by immunoglobulins containing terminal α-2,6-sialic acid linkages at the Asn297-linked glycan of the Fc region (sIVIg) [18]. Several preclinical model systems have provided evidence of the important role of sIVIg in determining the therapeutic activity of IVIg in rheumatoid arthritis, allergic airway disease, and autoimmune neurological disorders [19–22]. Therefore, sIVIg is considered a critical therapeutic strategy for attenuating pathogenic autoimmunity.
Antibody glycosylation directs innate and adaptive immune collaboration
2022, Current Opinion in ImmunologyCitation Excerpt :Sialylated antibodies have an anti-inflammatory effect. A number of research groups have proposed different mechanisms for this effect (Figure 1) thus it is not yet precisely clear how sialylation induces an anti-inflammatory bias [23–26]. Specific trends in antibody glycosylation have been identified in numerous contexts such as age, pregnancy, vaccination, infection, and autoimmune diseases [18].
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Supported by Talecris and Grifols Bio-therapeutics (Clinical Investigation Program) and the Canadian Institutes for Health Research (CIHR grants ISO115295 [to B.D.M.] and MOP67211 [to C.A.P.]), The Research Institute of the McGill University Health Center (RI-MUHC), the Montreal Chest Institute, and the Strauss Family Foundation. A.H.M. was the recipient of a Fonds de Recherche en Santé du Québec (FRSQ) Student Scholarship. B.D.M. is a Chercheur National of the FRSQ. C.A.P. holds a CIHR Canada Research Chair.
Disclosure of potential conflict of interest: A. H. Massoud has received research support from the Canadian Institute for Health Research (CIHR). F. Chouiali has received research support. H. Alturaihi has received research support from CIHR. C. A. Piccirillo has received consultant fees from GlaxoSmithKline, is employed by McGill University and Research Institute MUHC, and has provided expert testimony for the Montreal Law Firm. B. D. Mazer has received grants from Grifols Biotherapeutics and the CIHR and has grants/grants pending and has received payment for lectures including service on speakers' bureaus from Novartis. The rest of the authors declare that they have no relevant conflicts of interest.