Stromal cell-derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis.

The secreted protein developmental endothelial locus 1 (DEL-1) regulates inflammatory cell recruitment and protects against inflammatory pathologies in animal models. Here, we investigated DEL-1 in inflammatory arthritis using collagen-induced arthritis (CIA) and collagen Ab-induced arthritis (CAIA) models. In both models, mice with endothelium-specific overexpression of DEL-1 were protected from arthritis relative to WT controls, whereas arthritis was exacerbated in DEL-1-deficient mice. Compared with WT controls, mice with collagen VI promoter-driven overexpression of DEL-1 in mesenchymal cells were protected against CIA but not CAIA, suggesting a role for DEL-1 in the induction of the arthritogenic Ab response. Indeed, DEL-1 was expressed in perivascular stromal cells of the lymph nodes and inhibited Tfh and germinal center B cell responses. Mechanistically, DEL-1 inhibited DC-dependent induction of Tfh cells by targeting the LFA-1 integrin on T cells. Overall, DEL-1 restrained arthritis through a dual mechanism, one acting locally in the joints and associated with the anti-recruitment function of endothelial cell-derived DEL-1; the other mechanism acting systemically in the lymph nodes and associated with the ability of stromal cell-derived DEL-1 to restrain Tfh responses. DEL-1 may therefore be a promising therapeutic for the treatment of inflammatory arthritis.

Phytoestrogen-containing diets offer benefits for mouse embryology but lead to fewer offspring being produced.

One of the most commonly used protein sources in rodent diets is soy, which is naturally rich in phytoestrogens. Although phytoestrogens have shown potential health benefits in humans, they may also have the ability to disrupt reproduction. Consequently, there has been a tendency to try to exclude them from rodent diets. In the current study, we investigated whether phytoestrogen content in the mouse diet could affect reproduction in mice used as embryo donors. Donor mice (C57BL/6JOlaHsd) were maintained with three different diets: high phytoestrogen (ca. 400 mg/kg genistein), low phytoestrogen (ca. 10 mg/kg genistein) and standard breeding diet (ca. 120 mg/kg genistein). Mice fed a high phytoestrogen diet had a high yield of plugs, embryos, and injectable embryos, as well as producing good quality embryos. Results from donor mice fed a low phytoestrogen diet were consistently but only slightly inferior, whereas mice fed a standard diet performed the poorest. Interestingly, the largest number of born and weaned offspring were observed when recipient females received embryos from the standard diet group. Sperm yield and quality of stud males did not differ between the groups. We surmize that for experimental endpoints requiring fertilized embryos it may be more beneficial to feed mice a diet containing phytoestrogen, but if the goal is to produce transgenic mice, a diet high in phytoestrogen may be inadvisable. In conclusion, care should be taken when selecting a diet for experimental mouse colonies as phytoestrogen could influence the study outcome.