GIMAP/EA3064, Université de Lyon, Saint-Etienne, France.
Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, Paris, France.
Eur J Immunol. 2020 Sep;50(9):1295-1306. doi: 10.1002/eji.201948177. Epub 2020 Apr 28.
Human IgA could be from different isotypes (IgA1/IgA2) and/or isoforms (monomeric, dimeric, or secretory). Monomeric IgA mainly IgA1 are considered as an anti-inflammatory isotype whereas dimeric/secretory IgA have clearly dual pro- and anti-inflammatory effects. Here, we show that IgA isotypes and isoforms display different binding abilities to FcαRI, Dectin-1, DC-SIGN, and CD71 on monocyte-derived dendritic cells (moDC). We describe that IgA regulate the expression of their own receptors and trigger modulation of moDC maturation. We also demonstrate that dimeric IgA2 and IgA1 induce different inflammatory responses leading to cytotoxic CD8 T cells activation. moDC stimulation by dimeric IgA2 was followed by a strong pro-inflammatory effect. Our study highlights differences regarding IgA isotypes and isoforms in the context of DC conditioning. Further investigations are needed on the activation of adaptive immunity by IgA in the context of microbiota/IgA complexes during antibody-mediated immune selection.
人 IgA 可以来自不同的同型（IgA1/IgA2）和/或同种型（单体、二聚体或分泌型）。单体 IgA 主要是 IgA1 被认为是一种抗炎同型，而二聚体/分泌型 IgA 具有明显的双重促炎和抗炎作用。在这里，我们表明 IgA 同型和同种型在单核细胞衍生的树突状细胞（moDC）上显示出对 FcαRI、Dectin-1、DC-SIGN 和 CD71 的不同结合能力。我们描述了 IgA 调节其自身受体的表达，并触发 moDC 成熟的调节。我们还证明了二聚体 IgA2 和 IgA1 诱导不同的炎症反应，导致细胞毒性 CD8 T 细胞激活。二聚体 IgA2 刺激 moDC 后会产生强烈的促炎作用。我们的研究强调了 DC 调理中 IgA 同型和同种型的差异。需要进一步研究在抗体介导的免疫选择过程中，微生物群/IgA 复合物背景下，IgA 对适应性免疫的激活作用。
