Immunoglobulin A (IgA) is the most abundantly produced antibody isotype in mammals. The primary function of IgA is to maintain homeostasis at mucosal surfaces and play a role in immune protection. IgA functions mainly through interaction with multiple receptors including IgA Fc receptor I (FcαRI), transferrin receptor 1 (CD71), asialoglycoprotein receptor (ASGPR), Fcα/μR, FcRL4, and DC-SIGN/SIGNR1. In this review we discuss recent data demonstrating anti-inflammatory functions of IgA through two receptors, the FcαRI and DC-SIGN/SIGNR1 interactions in the regulation of immunity. Serum monomeric IgA is able to mediate an inhibitory signal following the interaction with FcαRI. It results in partial phosphorylation of its FcRγ-ITAM and the recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition following the formation of intracellular clusters named inhibisomes. In contrast, cross-linking of FcαRI by multimeric ligands induces a full phosphorylation of the FcRγ-ITAM leading to the recruitment of the tyrosine kinase Syk and cell activation. In addition, secretory IgA can mediate a potent anti-inflammatory function following the sugar-dependent interaction with SIGNR1 on dendritic cells which induces an immune tolerance via regulatory T cell expansion. Overall, the anti-inflammatory effect of serum and secretory IgA plays a crucial role in the physiology and in the prevention of tissue damage in multiple autoimmune and inflammatory diseases.