Nlrp3-dependent IL-1β inhibits CD103+ dendritic cell differentiation in the gut

The role of the microbiome and the NLRP3 inflammasome in the gut and lung

“…Together, these findings show that commensal bacteria, specific proteins derived from these bacteria, and Gram‐negative bacteria can directly activate inflammasomes in immune cells in an NLRP3‐dependent manner, partially through the activation of IRGB10. A recent study demonstrated that Nlrp3 −/− Rag −/− (T and B cell deficient) mice were protected against a T cell transfer colitis model by reducing Th17‐driven inflammation and IL‐1β and IL‐18 levels 42 . Although Rag −/− mice cohoused with Nlrp3 −/− Rag −/− mice had fecal microbiota profiles that shifted toward those exhibited by Nlrp3 −/− Rag −/− mice, with increased Rikenellaceae and decreased Bacteroidaceae , these taxa were also present in Nlrp3 −/− mice and cohousing did not alleviate disease 42 .…”

“…A recent study demonstrated that Nlrp3 −/− Rag −/− (T and B cell deficient) mice were protected against a T cell transfer colitis model by reducing Th17‐driven inflammation and IL‐1β and IL‐18 levels 42 . Although Rag −/− mice cohoused with Nlrp3 −/− Rag −/− mice had fecal microbiota profiles that shifted toward those exhibited by Nlrp3 −/− Rag −/− mice, with increased Rikenellaceae and decreased Bacteroidaceae , these taxa were also present in Nlrp3 −/− mice and cohousing did not alleviate disease 42 . Thus, these data demonstrate that NLRP3 inflammasome responses, and not necessarily intestinal dysbiosis caused by NLRP3 deletion, are responsible for improving colitis 42 …”

Toll-like receptor 2 impacts the development of oral tolerance in mouse pups via a milk-dependent mechanism

“…Because tolerogenic DC and Treg cells can play a crucial role in immune tolerance, TLR2 1/pups fed by either WT and TLR2 -/dams were assessed for populations of both of these cell types in the GALT at weaning (21 days), as shown in Fig 2, A. Tolerogenic DCs have been characterized in previous studies as MHC-II 1 CD11c 1 CD103 1 cells. 38 Feeding with milk from WT dams significantly increased the numbers of tolerogenic DCs in the MLNs and the spleen in cross-fostered pups compared with the numbers in their biologic siblings fed by TLR2 -/dams (Fig 2, C and D). The levels of tolerogenic DCs in the PP were not significantly different between pups nursed by WT or TLR2 -/dams (P 5 .834; data not shown).…”

“…Before extracellular or intracellular staining, single-cell suspensions were incubated with the fixable viability dye (FVD) eFluor 450 (ThermoFisher) diluted 1:1000 in PBS for 20 minutes at 48C. To determine the frequencies of DCs (adapted from Mak'Anyengo et al 38 ) and ILCs (adapted from Tait Wojno and Beamer 39 ) subsets, the cells were stained with a cocktail of antibodies for extracellular markers indicated in (see Table E1 in this article's Online Repository at www.jacionline.org). To identify subsets of T H cells, the cells were stimulated with 50 ng/mL of phorbol myristate acetate and 1 mg/mL of ionomycin in 10% FBS-RPMI medium for 5 hours before the addition of 13 Brefeldin A (ThermoFisher) for another hour.…”

Wheat-derived arabinoxylans reduced M2-macrophage functional activity, but enhanced monocyte-recruitment capacity

“…In contrast, CCL20 is essential for migration of CCR6-positive T H 17 cells towards the intestine, 34 a cell type linked to chronic inflammatory disease, 35 and IL-1β is crucial for Th17 polarization. 36 Moreover, CCL24 was shown to induce inflammatory infiltration of eosinophils, neutrophils and basophils 37 and CXCL8 has been shown to induce migration and activation of a large variety of immune cells. 38 Conditioned medium from wheat-AX-treated macrophages instigated monocyte migration equal to the conditioned medium from M1-like macrophages (Fig.…”