scholarly journals Development of follicular dendritic cells in lymph nodes depends on retinoic acid mediated signaling

Development ◽  
2021 ◽  
Author(s):  
Jasper J. Koning ◽  
Anusha Rajaraman ◽  
Rogier M. Reijmers ◽  
Tanja Konijn ◽  
Junliang Pan ◽  
...  

Specialized stromal cells occupy and help define B- and T cell domains, which is crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF-receptors is crucial for development of different stromal subsets, which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known. Using in vitro cultures of embryonic mouse stromal cells, we show that retinoic acid mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, while blocking lymphotoxin mediated Ccl19pos fibroblastic reticular cell (FRC) lineage differentiation. Accordingly, at day of birth we observe the presence of Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes. Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, while in addition, complete blockade of retinoic acid signaling prevents formation of FDC networks in lymph nodes.

2020 ◽  
Author(s):  
Jasper J. Koning ◽  
Anusha Rajaraman ◽  
Rogier M. Reijmers ◽  
Tanja Konijn ◽  
Junliang Pan ◽  
...  

AbstractSpecialized stromal cells occupy and help define B- and T cell domains, which is crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF-receptors is crucial for development of different stromal subsets which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known.Here we show that in mice, retinoic acid mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, while blocking lymphotoxin mediated Ccl19pos fibroblastic reticular cell (FRC) lineage differentiation. Consequently, we see at day of birth Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes.Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, while in addition, complete blockade of retinoic acid signaling prevents formation of FDC networks in lymph nodes.


1997 ◽  
Vol 288 (2) ◽  
pp. 381-389 ◽  
Author(s):  
Rikiya Tsunoda ◽  
Alain Bosseloir ◽  
Kikuo Onozaki ◽  
Ernst Heinen ◽  
Katsuya Miyake ◽  
...  

2020 ◽  
Vol 133 (16) ◽  
pp. jcs242883
Author(s):  
Xuan Luo ◽  
Valentine Seveau de Noray ◽  
Laurene Aoun ◽  
Martine Biarnes-Pelicot ◽  
Pierre-Olivier Strale ◽  
...  

ABSTRACTCell guidance by anchored molecules, or haptotaxis, is crucial in development, immunology and cancer. Adhesive haptotaxis, or guidance by adhesion molecules, is well established for mesenchymal cells such as fibroblasts, whereas its existence remains unreported for amoeboid cells that require less or no adhesion in order to migrate. We show that, in vitro, amoeboid human T lymphocytes develop adhesive haptotaxis mediated by densities of integrin ligands expressed by high endothelial venules. Moreover, lymphocytes orient towards increasing adhesion with VLA-4 integrins (also known as integrin α4β1), like all mesenchymal cells, but towards decreasing adhesion with LFA-1 integrins (also known as integrin αLβ4), which has not previously been observed. This counterintuitive ‘reverse haptotaxis’ cannot be explained by existing mechanisms of mesenchymal haptotaxis involving either competitive anchoring of cell edges under tension or differential integrin-activated growth of lamellipodia, because they both favor orientation towards increasing adhesion. The mechanisms and functions of amoeboid adhesive haptotaxis remain unclear; however, multidirectional integrin-mediated haptotaxis might operate around transmigration ports on endothelia, stromal cells in lymph nodes, and inflamed tissue where integrin ligands are spatially modulated.


2001 ◽  
Vol 34 (4) ◽  
pp. 265-273 ◽  
Author(s):  
Yoshiaki Ohmori ◽  
Toshiko Yoshida ◽  
Motonori Okabe ◽  
Kenichi Takaya ◽  
Fumitomo Koizumi ◽  
...  

2019 ◽  
Vol 95 (2) ◽  
pp. 202-208
Author(s):  
Yusuke Sumitani ◽  
Kenta Uchibe ◽  
Kaya Yoshida ◽  
Yao Weng ◽  
Jiajie Guo ◽  
...  

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3529-3536 ◽  
Author(s):  
Hui Wang ◽  
Xuan Zheng ◽  
Frederick G. Behm ◽  
Manohar Ratnam

Abstract Folate receptor (FR) type β is expressed in the myelomonocytic lineage, predominantly during neutrophil maturation and in myeloid leukemias. FR-β expression was elevated up to 20-fold by all-trans retinoic acid (ATRA) in KG-1 myeloid leukemia cells in a dose-dependent and reversible manner in the absence of terminal differentiation or cell growth inhibition. ATRA also increased FR-β expression in vitro in myeloid leukemia cells from patient marrow. FR-β was not up-regulated in KG-1 cells treated with phorbol ester, dexamethasone, 1,25-dihydroxy vitamin D3, or transforming growth factor β. ATRA did not induce FR-β expression in receptor negative cells of diverse origin. The ATRA-induced increase in FR-β expression in KG-1 cells occurred at the level of messenger RNA synthesis, and in 293 cells containing a stably integrated FR-β promoter–luciferase reporter construct, ATRA induced expression of the reporter. From experiments using retinoid agonists and antagonists and from cotransfection studies using the FR-β promoter and expression plasmids for the nuclear receptors retinoic acid receptor (RAR)α, RARβ, or RARγ, it appears that the retinoid effect on FR-β expression could be mediated by ligand binding to RARs α, β, or γ, but not to retinoid X receptors. Furthermore, there was apparent cross-talk between RARα and RARγ selective agonists or antagonists, suggesting a common downstream target for RAR isoforms in inducing FR-β expression. Thus, blocks in the RARα-specific pathway of retinoid-induced differentiation may be bypassed during retinoid induction of FR-β expression. The results suggest that to facilitate FR-targeted therapies, retinoids may be used to modulate FR-β expression in myeloid leukemia cells refractory to retinoid differentiation therapy.


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