Comparative safety and efficacy of ozanimod versus fingolimod for relapsing multiple sclerosis.

Ozanimod and fingolimod are sphingosine 1-phosphate receptor-modulating therapies for relapsing multiple sclerosis. Comparative effectiveness was assessed by matching adjusted indirect comparisons of safety and efficacy trial outcomes at first-dose cardiac monitoring, 1 year and 2 years. After adjustment, baseline characteristics were similar.

Distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP.

How lipopolysaccharide (LPS) signals through toll-like receptors (TLRs) to induce nuclear factor (NF)-kappa B inflammatory cytokines in sepsis remains unclear. Major candidates for that process are myeloid differentiation protein 88 (MyD88) and MyD88 adaptor-like/TIR domain-containing adaptor protein (Mal/TIRAP) but their role needs to be further defined. Here, we have examined the role of MyD88 and Mal/TIRAP in primary human cells of nonmyeloid and myeloid origin as physiologically relevant systems.

Transient inhibition of interleukin 4 signaling by T cell receptor ligation.

Interleukin (IL)-4 and IL-12 together with T cell receptor (TCR) engagement are crucial for the differentiation of CD4(+) T cells into T helper (Th)2 or Th1 cells, respectively. Although IL-4 receptors (IL-4Rs) but not IL-12Rs are expressed on naive CD4(+) T cells, IL-4 has no apparent advantage over IL-12 in driving naive T cell differentiation when the cells are primed with both IL-4 and IL-12 in vitro. It was found that IL-4-induced phosphorylation of Janus kinases 1 and 3, IL-4R alpha, signal transducer and activator of transcription 6, and insulin receptor substrate 2 was strikingly but transiently inhibited by TCR ligation both in conventional and TCR transgenic T cells.

Novel molecular mechanisms of dendritic cell-induced T cell activation.

In this study we have re-examined the molecular mechanisms involved in activation of T cells by dendritic cells (DC). Human peripheral blood DC (PBDC) were derived by 2 h adhesion followed by 7 day culture in a combination of granulocyte macrophage colony stimulating factor and IL-4, and depletion of residual T and B cells. These PBDC were used to induce autologous T cell proliferation in a CD3-dependent response, and antibodies against CD11a/18 and CD86 were used as control inhibitors of accessory function.

Expression of retinoid receptors during human monocyte differentiation in vitro.

1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)VD(3)) and retinoic acid (RA) modulate the activation of monocytes (MO) and their differentiation into macrophages (MAC). As these effects are mostly mediated by heterodimers or homodimers of the specific nuclear receptors for 1,25(OH)(2)VD(3) and RA, we investigated the expression of the retinoic acid receptors (RAR) alpha, beta, and gamma and the retinoid X-receptor (RXR) alpha in MO during differentiation into MAC or dendritic cells (DC). The mRNA of all investigated receptors except RARbeta was detected in short-term cultured MO.