| First Author | Yokota-Nakatsuma A | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 37914 | PubMed ID | 27897208 |
| Mgi Jnum | J:287385 | Mgi Id | MGI:6407497 |
| Doi | 10.1038/srep37914 | Citation | Yokota-Nakatsuma A, et al. (2016) Beta 1-integrin ligation and TLR ligation enhance GM-CSF-induced ALDH1A2 expression in dendritic cells, but differentially regulate their anti-inflammatory properties. Sci Rep 6:37914 |
| abstractText | Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80. The TLR-L-treated DCs produced proinflammatory cytokines unlike normal ALDH1A2(high) MLN-DCs, whereas the E-cadherin-treated DCs did not. Immobilized VCAM-1 and semaphorin 7 A exerted effects similar to those of E-cadherin. Soluble anti-integrin beta1 antibodies or inhibitors of integrin signaling molecules suppressed the effects of these immobilized proteins, whereas immobilized anti-integrin beta1 antibodies enhanced the GM-CSF/Am80-induced ALDH1A2 expression without inducing proinflammatory cytokines. Sequential stimulation of splenic pre-DCs with GM-CSF/Am80 and immobilized E-cadherin or anti-integrin beta1 antibody also induced differentiation to mature DCs with high ALDH activity. The E-cadherin-treated BM-DCs induced gut-tropic Foxp3(+) T cells and alleviated DSS-induced colitis, whereas the TLR-L-treated DCs aggravated DSS-induced colitis. The results suggest that integrin beta1-mediated signals contribute to the differentiation and maturation of RA-producing anti-inflammatory DCs. |
