Immunological Function of Sphingosine 1-Phosphate in the Intestine

It has been shown that dietary materials are involved in immune regulation in the intestine. Lipids mediate immune regulation through a complex metabolic network that produces many kinds of lipid mediators. Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. In this review, we focus on the immunological functions of S1P in the regulation of intestinal immune responses such as immunoglobulin A production and unique T cell trafficking, and its role in the development of intestinal immune diseases such as food allergies and intestinal inflammation, and also discuss the relationship between dietary materials and S1P metabolism

Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice

Toll-like receptors (TLRs) have a crucial role in sensing microbial products and triggering immune responses. Recent reports have indicated that TLR7 and TLR9 have an important role in activating autoreactive B cells. In addition to TLR7 and TLR9, mouse B cells express TLR2, TLR4 and structurally related Radioprotective105 (RP105). We have previously shown that RP105 works in concert with TLR2/4 in antibody response to TLR2/4 ligands. We here report that B cells are constitutively activated by TLR2/4 and RP105. Such B cell activation was revealed by the γ3 germ line transcript and serum IgG3 production, both of which were impaired by the lack of RP105 or TLR2/4. Serum IgG3 was not altered in germ-free or antibiotics-treated mice, suggesting that the microbial flora hardly contributes to the continuous activation of B cells. The lack of RP105-dependent B cell activation ameliorated disease progression in lupus-prone MRL/lpr mice. RP105−/− MRL/lpr mice showed less lymphoadenopathy/splenomegaly and longer survival than MRL/lpr mice. Whereas glomerulonephritis and auto-antibody production were not altered, improvement in blood urea nitrogen and lower incidence of renal arteritis indicated that renal function was ameliorated in the absence of RP105. Our results suggest that RP105-dependent tonic B cell activation has a pathogenic role in MRL/lpr mic

Characteristics of claudin expression in follicle-associated epithelium of Peyer's patches: Preferential localization of claudin-4 at the apex of the dome region

Gut-associated lymphoreticular tissue (GALT), such as Peyer's patches (PP) and cecal patches, are important inductive sites for mucosal immune responses. As such, the GALT may have an epithelial barrier different from that of villous epithelium. In this study, we investigated the immunohistochemical distribution of the claudin family and occludin in the follicle-associated epithelium (FAE) of Peyer's patches and cecal patches of murine intestine. Unique profiles of claudin-2, -3, -4 and occludin expression were noted in the tight junctions of the FAE: claudin-4 was preferentially expressed in the apex region; claudin-2 was only weakly expressed on the crypt side of the FAE compared to stronger expression on the crypt side of villous epithelial cells; claudin-3 and occludin were found throughout the dome. These unique expression patterns were present also in cecal patch FAE. We also found that claudin-4 expression in the FAE of Peyer's patches and cecal patches corresponded with the presence of TUNEL-positive apoptotic cells, and Peyer's patch-deficient mice had expression patterns of claudin and occludin in villous epithelia similar to those in wild-type mice. We conclude that claudin-4 expression is preferentially associated with the dome region of FAE, the mucosal inductive site of the murine intestine. In that location and it might correlate with the cell life cycle, help maintain the apex configuration of the dome, or be a factor favoring the uptake of antigens by the FAE

Initiation of NALT Organogenesis Is Independent of the IL-7R, LTβR, and NIK Signaling Pathways but Requires the Id2 Gene and CD3−CD4+CD45+ Cells

AbstractInitiation of nasopharyngeal-associated lymphoid tissue (NALT) development is independent of the programmed cytokine cascade necessary for the formation of Peyer's patches (PP) and peripheral lymph nodes (PLN), a cytokine cascade which consists of IL-7R, LTα1β2/LTβR, and NIK. However, the subsequent organization of NALT seems to be controlled by these cytokine signaling cascades since the maturation of NALT structure is generally incomplete in those cytokine cascade-deficient mice. NALT as well as PP and PLN are completely absent in Id2−/− mice. NALT organogenesis is initiated following the adoptive transfer of CD3−CD4+CD45+ cells into Id2−/− mice, constituting direct evidence that CD3−CD4+CD45+ inducer cells can provide an IL-7R-, LTα1β2/LTβR-, and NIK-independent tissue organogenesis pathway for secondary lymphoid tissue development