title: Monomeric Immunoglobulin A from Plasma Inhibits Human Th17 ResponsesIn VitroIndependent of FcαRI and DC-SIGN.
abstract: Circulating immunoglobulins including immunoglobulin G (IgG) and IgM play a critical role in the immune homeostasis by modulating functions of immune cells. These functions are mediated in part by natural antibodies. However, despite being second most abundant antibody in the circulation, the immunoregulatory function of IgA is relatively unexplored. As Th17 cells are the key mediators of a variety of autoimmune, inflammatory, and allergic diseases, we investigated the ability of monomeric IgA (mIgA) isolated from pooled plasma of healthy donors to modulate human Th17 cells. We show that mIgA inhibits differentiation and amplification of human Th17 cells and the production of their effector cytokine IL-17A. mIgA also suppresses IFN-γ responses under these experimental conditions. Suppressive effect of mIgA on Th17 responses is associated with reciprocal expansion of FoxP3-positive regulatory T cells. The effect of mIgA on Th17 cells is dependent on F(ab')2fragments and independent of FcαRI (CD89) and DC-SIGN. Mechanistically, the modulatory effect of mIgA on Th17 cells implicates suppression of phosphorylation of signal transducer and activator of transcription 3. Furthermore, mIgA binds to CD4+T cells and recognizes in a dose-dependent manner the receptors for cytokines (IL-6Rα and IL-1RI) that mediate Th17 responses. Our findings thus reveal novel anti-inflammatory functions of IgA and suggest potential therapeutic utility of mIgA in autoimmune and inflammatory diseases that implicate Th17 cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale , Paris , France.
authors.forename: Chaitrali
authors.initials: C
authors.lastname: Saha
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Mrinmoy
authors.initials: M
authors.lastname: Das
authors.affiliation: Institut National de la Santé et de la Recherche Médicale , Paris , France.
authors.forename: Veerupaxagouda
authors.initials: V
authors.lastname: Patil
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stephen-Victor
authors.affiliation: Institut National de la Santé et de la Recherche Médicale , Paris , France.
authors.forename: Meenu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Research Department, CSL Behring AG , Bern , Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Wymann
authors.affiliation: Research Department, CSL Behring AG , Bern , Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Jordi
authors.affiliation: Research Department, CSL Behring AG , Bern , Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Vonarburg
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche des Cordeliers, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
keywords: CD89; DC-SIGN; FcαRI; IL-17; IVIG; Th17; Treg; monomeric IgA; natural antibodies