Enhanced anti-serpin antibody activity inhibits autoimmune inflammation in type 1 diabetes.

Intracellular (clade B) OVA-serpin protease inhibitors play an important role in tissue homeostasis by protecting cells from death in response to hypo-osmotic stress, heat shock, and other stimuli. It is not known whether these serpins influence immunological tolerance and the risk for autoimmune diseases. We found that a fraction of young autoimmune diabetes-prone NOD mice had elevated levels of autoantibodies against a member of clade B family known as serpinB13.

EBI3 deficiency leads to diminished T helper type 1 and increased T helper type 2 mediated airway inflammation.

Despite extensive investigation of the signals required for development of T helper type 1 (Th1) and type 2 (Th2) immune responses, the mechanisms involved are still not well-defined. A critical role for Epstein-Barr virus-induced gene 3 (EBI3) in these responses has been proposed. EBI3, initially discovered as a transcriptionally activated gene in Epstein-Barr virus-infected B lymphocytes, codes for a subunit of the cytokine interleukin-27 (IL-27).

Targeting Toll-like receptors on dendritic cells modifies the T(H)2 response to peanut allergens in vitro.

Background: Delivery of allergens with bacterial adjuvants has been shown to be a successful immunotherapeutic strategy for food allergy treatment in animal models. How microbial signals, acting through the innate immune system, reshape ongoing allergic responses is poorly understood.

Objective: To investigate the contribution of Toll-like receptors (TLRs) in the response to bacterial adjuvants, we designed an in vitro system to characterize the effect of heat-killed Escherichia coli vector (HKE) on peanut-induced responses of dendritic cells (DCs) and T cells.

Lung vascular endothelial growth factor expression induces local myeloid dendritic cell activation.

We previously demonstrated that vascular endothelial growth factor (VEGF) expression in the murine lung increases local CD11c+MHCII+ DC number and activation. In this study, employing a multicolor flow cytometry, we report increases in both myeloid (mDC) and plasmacytoid (pDC) DC in the lungs of VEGF transgenic (tg) compared to WT mice. Lung pDC from VEGF tg mice exhibited higher levels of activation with increased expression of MHCII and costimulatory molecules.

p21 Ras/impedes mitogenic signal propagation regulates cytokine production and migration in CD4 T cells.

The propensity of T cells to generate coordinated cytokine responses is critical for the host to develop resistance to pathogens while maintaining the state of immunotolerance to self-antigens. The exact mechanisms responsible for preventing the overproduction of proinflammatory cytokines including interferon (IFN)-gamma are not fully understood, however. In this study, we examined the role of a recently described Ras GTPase effector and repressor of the Raf/MEK/ERK cascade called impedes mitogenic signal propagation (Imp) in limiting the induction of T-cell cytokines.