Butyrate and retinoic acid imprint mucosal-like dendritic cell development synergistically from bone marrow cells

Abstract

SummaryAccumulating data show that the phenotypes and functions of distinctive mucosal dendritic cells (DCs) in the gut are regulated by retinoic acid (RA). Unfortunately, the exact role of butyrate in RA-mediated mucosal DC differentiation has not been elucidated thoroughly to date. Mucosal-like dendritic cell differentiation was completed in vitro by culturing bone marrow cells with growth factors [granulocyte-macrophage colonystimulating factor (GM-CSF/interleukin (IL)-4], RA and/or butyrate. The phenotypes, cytokine secretion, immune functions and levels of retinal dehydrogenase of different DCs were detected using quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The results showed that RA-induced DCs (RADCs) showed mucosal DC properties, including expression of CD103 and gut homing receptor a 4 b 7 , low proinflammatory cytokine secretion and low priming capability to antigen-specific CD4 1 T cells. Butyrate-treated RADCs (Bu-RA-DCs) decreased CD11c, but increased CD103 and a 4 b 7 expression. Moreover, the CD4 1 T priming capability and the levels of retinal dehydrogenase of RA-DCs were suppressed significantly by butyrate. Thus, butyrate and retinoic acid have different but synergistic regulatory functions on mucosal DC differentiation, indicating that immune homeostasis in the gut depends largely upon RA and butyrate to imprint different mucosal DC subsets, both individually and collectively.

Microbial signature in IgE-mediated food allergies

“…It was also reported that a high-fiber diet could promote oral tolerance and confer protection against FA in mice via SCFA signaling through several pathways, such as G-protein-coupled receptor GPR43 signaling [ 4 , 7 ], mediated by acetate and propionate [ 8 , 9 ]. On a cellular level, SCFAs act to promote the development of tolerogenic CD103 + dendritic cells, which influence the development of regulatory T cells [ 10 ] and drive B cell production of IgA [ 11 ]. Conversely, immune dysregulation may result from changes in the gut microbiota composition [ 12 ] leading to changes in the above cellular milieu, and in the case of allergy leading to production of Th2 cytokines and food allergen-specific IgE [ 13 ].…”

Synthesis of peptide conjugates with vitamins for induction of antigen‐specific immunotolerance

“…These results indicate that free ATRA is released from 1 in DC2.4 cells to induce suppressive effects against an LPS-induced inflammatory response, which are consistent with previous reports describing the response of bone marrow derived DCs to ATRA. [29][30][31] The expression of antiinflammatory cytokine, TGF-β was not affected by ATRA and Conjugate 1, whereas another anti-inflammatory cytokine, IL-10 was reduced. A similar response in IL-10 production of DCs stimulated by ATRA was reported previously.…”

The Butyrogenic and Lactic Bacteria of the Gut Microbiota Determine the Outcome of Allogenic Hematopoietic Cell Transplant

“…Vitamin A is taken from food in the form of retinol, retinoic acid, or beta-carotene. In the gut, dendritic cells (DCs) metabolize vitamin A in RA, and RA co-operates with butyrate to induce mucosal-like CD103 + DCs differentiation required to trigger the differentiation and intestinal recruitment of FoxP3 + T regulator (T reg) cells, IgA antibody secretion, and reduce inflammation (Qiang et al, 2017). The butyrate receptors, FFA2/GPR43 and FFA3/ GPR41, are all found expressed on liver cells.…”