Immune Complexes Indirectly Suppress the Generation of Th17 Responses In Vivo

Abstract

The precise context in which the innate immune system is activated plays a pivotal role in the subsequent instruction of CD4+ T helper (Th) cell responses. Th1 responses are downregulated when antigen is encountered in the presence of antigen-IgG immune complexes. To assess if Th17 responses to antigen are subject to similar influences in the presence of immune complexes we utilized an inflammatory airway disease model in which immunization of mice with Complete Freund’s Adjuvant (CFA) and ovalbumin (Ova) induces a powerful Ova-specific Th1 and Th17 response. Here we show that modification of that immunization with CFA to include IgG-Ova immune complexes results in the suppression of CFA-induced Th17 responses and a concurrent enhancement of Ova-specific Th2 responses. Furthermore, we show the mechanism by which these immune complexes suppress Th17 responses is through the enhancement of IL-10 production. In addition, the generation of Th17 responses following immunization with CFA and Ova were dependent on IL-1α but independent of NLRP3 inflammasome activation. Together these data represent a novel mechanism by which the generation of Th17 responses is regulated.

Sphingosine 1‐Phosphate Receptor 1 Signaling Maintains Endothelial Cell Barrier Function and Protects Against Immune Complex–Induced Vascular Injury

“…After washing in cold PBS, the pellet was resuspended in 300 ll PBS. Previous work by other laboratories has shown that goat IgG binds human and mouse Fc receptors (20,21).…”

“…Previous work by other laboratories has shown that goat IgG binds human and mouse Fc receptors [20, 21]. …”

Amelioration of Experimental autoimmune encephalomyelitis and DSS induced colitis by NTG-A-009 through the inhibition of Th1 and Th17 cells differentiation

“…Adjuvants act by targeting antigens to APCs thereby enhancing antigen presentation by MHC 48 . Presentation of antigens along with cytokine and co-stimulatory molecules drives the differentiation of naïve CD4 + T cells in effector cells 49 . So, we employed OVA based inflammatory model in mice, in which OVA was combined with CFA (complete Freund’s adjuvant) and induces powerful OVA specific Th1 and Th17 inflammatory immune response.…”

BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis

“…The environment in which APCs initially encounter antigens is associated with specific adjuvants. Presentation of processed antigen with co-stimulatory molecules and a precise combination of cytokines drives differentiation of naïve CD4 + T cells toward a specific effector lineage, including that of Th1, Th2 and Th17 cells [ 40 ]. Therefore, we used an OVA-based mouse inflammatory disease model in which OVA combined with CFA, a potent Th1/Th17 skewing adjuvant, induced a powerful Ova-specific Th1 and Th17 inflammatory immune response.…”