Stimulation Of IgA Research Articles

Carotenoids and Their Health Benefits as Derived via Their Interactions with Gut Microbiota.

Carotenoids have been related to a number of health benefits. Their dietary intake and circulating levels have been associated with a reduced incidence of obesity, diabetes, certain types of cancer, and even lower total mortality. Their potential interaction with the gut microbiota (GM) has been generally overlooked but may be of relevance, as carotenoids largely bypass absorption in the small intestine and are passed on to the colon, where they appear to be in part degraded into unknown metabolites. These may include apo-carotenoids that may have biological effects because of higher aqueous solubility and higher electrophilicity that could better target transcription factors, i.e., NF-κB, PPARγ, and RAR/RXRs. If absorbed in the colon, they could have both local and systemic effects. Certain microbes that may be supplemented were also reported to produce carotenoids in the colon. Although some bactericidal aspects of carotenoids have been shown in vitro, a few studies have also demonstrated a prebiotic-like effect, resulting in bacterial shifts with health-associated properties. Also, stimulation of IgA could play a role in this respect. Carotenoids may further contribute to mucosal and gut barrier health, such as stabilizing tight junctions. This review highlights potential gut-related health-beneficial effects of carotenoids and emphasizes the current research gaps regarding carotenoid-GM interactions.

Induction of interleukin‐10 expression through Fcα receptor in human monocytes and monocyte‐derived dendritic cells: role of p38 MAPKinase

As previously reported by others for immunoglobulin (Ig)G, we observed that IgA can induce interleukin (IL)-10 expression in human monocytes. In this study, we explored the molecular mechanisms of IL-10 induction by IgA in monocytes and monocyte-derived dendritic cells (MD-DCs). Monomeric IgA induced IL-10 production in monocytes and this production was further increased upon IgA cross-linking. Similar IL-10 responses were observed in monocytes and autologous MD-DCs, and were inhibited (by approximately 77%) by preincubation with a blocking mAb to FcalphaRI. IL-10 induction by IgA correlated with activation of MAPKinases ERK1/2, p38 and JNK, whereas only p38-inhibitor SB-203580 inhibited IL-10 induction. Upon IgA stimulation, AP-1, NFkappaB and Sp1 transcription factors were activated and inhibitors of NFkappaB and of Sp1 suppressed IgA-driven transcriptional activation of IL-10. In addition, p38 MAPK activation appeared that it was required to control nuclear translocation of NFkappaB and Sp1 upon IgA stimulation. Therefore, in human monocytes and MD-DCs the mechanisms of IL-10 induction by IgA involve p38 MAPK-dependent recruitment of both NFkappaB and Sp1.

Concentration-dependent bifunctional effect of TGF-β 1 on immunoglobulin production: a role for Smad3 in IgA production in vitro

Injury to the liver results in rapid induction of transforming growth factor-beta1 (TGF-β 1) consistent with a role for TGF-β 1 in repairing damaged tissue. In addition to its ubiquitous role in injury repair, TGF-β 1 is also well established as a critical regulator of immune homeostasis; however, its mechanisms of action remain enigmatic. We have previously demonstrated that the hepatotoxic chlorinated hydrocarbon, carbon tetrachloride, suppresses helper T-lymphocyte function in a TGF-β 1-dependent manner. Here, we report that, in opposition to its immunosuppressive effects at picomolar concentrations, femtomolar concentrations of TGF-β 1 augment T cell-dependent anti-sRBC IgM antibody forming cell (AFC) and T cell-independent DNP-Ficoll-induced AFC responses. These data support a concentration-dependent bifunctional effect by TGF-β 1 on humoral immune responses in vitro. We further investigated a putative mechanistic role for Smad3, an intracellular mediator of TGF-β 1 signaling, in propagating the inhibitory effects of TGF-β 1 on humoral immune responses. Relative to wild type littermates, splenocytes from mice homologous for a null mutation in the gene encoding the TGF-β receptor-activated Smad3 (Smad3 Exon8−/−) were less sensitive to inhibition by TGF-β 1 following anti-sRBC- and LPS-sensitization in vitro. In agreement, inhibition of IgM protein production by TGF-β 1 was also dampened in LPS-sensitized Smad3 Exon8−/− splenic B cells. Moreover, stimulation of IgA by TGF-β 1 was abrogated in LPS-sensitized Smad3 Exon8−/− splenocytes suggesting an additional role for Smad3 in regulating IgA production in vitro. Our results suggest that the effects of TGF-β 1 on humoral immune responses fundamentally differ in a concentration-dependent manner and are mediated, in part, through Smad3 signaling.

Hyper-immunoglobulin A in the hyperimmunoglobulinemia D syndrome.

The hyperimmunoglobulinemia D syndrome (HIDS) is an autosomal recessive disorder characterized by recurrent febrile attacks with abdominal, articular, and skin manifestations. Apart from elevated immunoglobulin D (IgD) levels (>100 IU/ml), there are high IgA levels in the majority of cases. Mutations in the gene encoding mevalonate kinase constitute the molecular defect in HIDS. The cause of elevated IgA concentrations in HIDS patients remains to be elucidated. We studied the hyper-IgA response in serum of a group of HIDS patients. Elevated IgA concentrations result from increased IgA1 concentrations. IgA and IgA1 concentrations correlated significantly with IgD concentrations, and levels of IgA polymers were significantly higher than the levels in healthy donors. These results indicate a continuous, presumably systemic, stimulation of IgA in HIDS patients.