Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2–dependent prostaglandin E2 in human dendritic cells

Abstract

production, and Treg expansion were mediated in part via interaction of IVIg and F(ab9) 2 fragments of IVIg with DC-specific intercellular adhesion molecule-3-grabbing nonintegrin. Our results thus uncover novel cellular and molecular mechanism by which IVIg expands Tregs.

Intravenous immunoglobulin-mediated expansion of regulatory T cells in autoimmune patients is associated with increased prostaglandin E2 levels in the circulation

“…Thus, these results corroborate our previous data indicating a role for DC-secreted PGE 2 in IVIg-mediated Treg expansion and, hence, validate the therapeutic relevance of our report. 8 Notably, the up-regulation of PGE 2 was also minimal in a patient who did not show Treg enhancement (Figure 1b). Therefore, these results indicate that Treg expansion by IVIg is directly linked to the amount of absolute increase in PGE 2 .…”

“…6,7 Recently, we demonstrated that IVIg-mediated Treg expansion requires the induction COX-2-dependent PGE 2 in human DCs. 8 The inhibition of COX-2 activity in DCs led to the abrogation of IVIg-mediated Treg expansion both in vitro and in vivo in an experimental autoimmune encephalomyelitis model. However, the effect of IVIg therapy on PGE 2 levels in autoimmune patients has not yet been investigated.…”

“…Based on previous reports, we propose that DCs and monocytes might be the primary contributors. 8,9 Currently, IVIg therapy is an established treatment of choice for GBS (level A recommendation). The available clinical data demonstrate that GBS patients who receive IVIg therapy within 2 weeks after the onset of this disease exhibit accelerated recovery.…”

“…8 Briefly, ELISA plates were incubated with plasma samples and serially diluted standards overnight at 4 uC. Following three washes with PBS-Tween (PBST) buffer, the plates were blocked with 1% BSA-PBST for 1 h at 37 uC.…”

Soluble molecules in intravenous immunoglobulin: benefits and limitations

“…[11] This expansion maybe partly via induction of cyclooxygenase (COX)-2-dependent prostaglandin E2 in antigenpresenting cells (APCs). [12] On the other hand, recent studies demonstrate that, regardless of the brand or the product batch, all IVIg preparations studied were found to equally inhibit the production of IL-17A from Th17 cells in vitro. [13] These observations suggest that the anti-inflammatory effect of IVIg helps to restore immune tolerance in autoimmune and inflammatory conditions.…”