Inhibition of the proteasome influences murine and human dendritic cell development in vitro and in vivo

Immunobiology ◽  
2009 ◽  
Vol 214 (9-10) ◽  
pp. 843-851 ◽  
Author(s):  
Elisabeth Zinser ◽  
Susanne Rößner ◽  
Leonie Littmann ◽  
Daniel Lüftenegger ◽  
Ulrich Schubert ◽  
...  
Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 961-969 ◽  
Author(s):  
Hideki Tsujimura ◽  
Tomohiko Tamura ◽  
Celine Gongora ◽  
Julio Aliberti ◽  
Caetano Reis e Sousa ◽  
...  

Abstract Dendritic cells (DCs) develop from bone marrow (BM) progenitor cells and mature in response to external signals to elicit functions important for innate and adaptive immunity. Interferon consensus sequence binding protein (ICSBP; also called interferon regulatory factor 8 [IRF-8]) is a hematopoietic cell–specific transcription factor expressed in BM progenitor cells that contributes to myeloid cell development. In light of our earlier observation that ICSBP−/− mice lack CD8α+DCs, we investigated the role of ICSBP in DC development in vitro in the presence of Flt3 ligand. Immature ICSBP−/− DCs developed from BM progenitor cells showed assorted defects, did not mature in response to activation signals, and failed to express CD8α and interleukin 12 (IL-12) p40, a feature consistent with ICSBP−/− DCs in vivo. We show that retroviral introduction of ICSBP restores the development of immature DCs that can fully mature on activation signals. All the defects seen with ICSBP−/− DCs were corrected after ICSBP transduction, including the expression of CD8α and IL-12 p40 as well as major histocompatability complex class II and other costimulatory molecules. ICSBP is known to regulate gene expression by interacting with partner proteins PU.1 and IRFs, thereby binding to target elements ISRE and EICE. Analysis of a series of ICSBP mutants showed that the intact DNA-binding activity as well as the ability to interact with partner proteins are required for the restoration of DC development/maturation, pointing to the transcriptional function of ICSBP as a basis of restoration. Taken together, this study identifies ICSBP as a factor critical for both early differentiation and final maturation of DCs.


2004 ◽  
Vol 78 ◽  
pp. 601-602
Author(s):  
S Ciesek ◽  
B P. Ringe ◽  
C P. Strassburg ◽  
J Klempnauer ◽  
M P. Manns ◽  
...  

Blood ◽  
2003 ◽  
Vol 102 (9) ◽  
pp. 3302-3310 ◽  
Author(s):  
A. Karolina Palucka ◽  
Joel Gatlin ◽  
Jean Philippe Blanck ◽  
Michael W. Melkus ◽  
Sandra Clayton ◽  
...  

AbstractDistinct human dendritic cell (DC) subsets differentially control immunity. Thus, insights into their in vivo functions are important to understand the launching and modulation of immune responses. We show that nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice engrafted with human CD34+ hematopoietic progenitors develop human myeloid and plasmacytoid DCs. The skin displays immature DCs expressing Langerin, while other tissues display interstitial DCs. Myeloid DCs from these mice induce proliferation of allogeneic CD4 T cells in vitro, and bone marrow human cells containing plasmacytoid DCs release interferon-α (IFN-α) upon influenza virus exposure. Injection of influenza virus into reconstituted mice triggers IFN-α release and maturation of mDCs. Thus, these mice may provide a model to study the pathophysiology of human DC subsets.


2019 ◽  
Vol 169 ◽  
pp. 111-120 ◽  
Author(s):  
Evelyne Schaeffer ◽  
Elena M. Sánchez-Fernández ◽  
Rita Gonçalves-Pereira ◽  
Vincent Flacher ◽  
Delphine Lamon ◽  
...  

Life Sciences ◽  
1989 ◽  
Vol 44 (13) ◽  
pp. v-xii ◽  
Author(s):  
J.W. Hadden ◽  
H. Chen ◽  
Y. Wang ◽  
A. Galy ◽  
E. Hadden

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hélène Letscher ◽  
Viviane A. Agbogan ◽  
Sarantis Korniotis ◽  
Pauline Gastineau ◽  
Emmanuel Tejerina ◽  
...  

AbstractEarly innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+ CD11b+ dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1451
Author(s):  
Carolina Romeiro Fernandes Chagas ◽  
Josef Harl ◽  
Vytautas Preikša ◽  
Dovilė Bukauskaitė ◽  
Mikas Ilgūnas ◽  
...  

Recent studies confirmed that some Hepatozoon-like blood parasites (Apicomplexa) of birds are closely related to the amphibian parasite Lankesterella minima. Little is known about the biology of these pathogens in birds, including their distribution, life cycles, specificity, vectors, and molecular characterization. Using blood samples of 641 birds from 16 species, we (i) determined the prevalence and molecular diversity of Lankesterella parasites in naturally infected birds; (ii) investigated the development of Lankesterella kabeeni in laboratory-reared mosquitoes, Culex pipiens forma molestus and Aedes aegypti; and (iii) tested experimentally the susceptibility of domestic canaries, Serinus canaria, to this parasite. This study combined molecular and morphological diagnostic methods and determined 11% prevalence of Lankesterella parasites in Acrocephalidae birds; 16 Lankesterella lineages with a certain degree of host specificity and two new species (Lankesterella vacuolata n. sp. and Lankesterella macrovacuolata n. sp.) were found and characterized. Lankesterella kabeeni (formerly Hepatozoon kabeeni) was re-described. Serinus canaria were resistant after various experimental exposures. Lankesterella sporozoites rapidly escaped from host cells in vitro. Sporozoites persisted for a long time in infected mosquitoes (up to 42 days post exposure). Our study demonstrated a high diversity of Lankesterella parasites in birds, and showed that several avian Hepatozoon-like parasites, in fact, belong to Lankesterella genus.


Development ◽  
1968 ◽  
Vol 19 (3) ◽  
pp. 407-414
Author(s):  
R. Christy Armstrong ◽  
Joel J. Elias

Abnormalities of the ocular system which appear in organ culture in Waymouth's medium with freshly added glutamine (Armstrong & Elias, 1968) resemble those caused by transitory pteryolglutamic acid (PGA or folic acid) deficiency in vivo (Armstrong & Monie, 1966). The configurations of such malformations as lens herniations, retinal diverticula, and rosette-like formations of the retina are remarkably similar in both cases. The experiments reported in this paper were undertaken in an effort to understand the mechanisms involved in the production of similar abnormalities by two very different experimental conditions: the addition of glutamine in vitro and the transitory deficiency of PGA in vivo. One series of experiments involved the effects of manipulation of the PGA and glutamine content of the culture medium on eye development in vitro. Parallel studies on PGA-deficiency in vivo were undertaken in conjunction with organ-culture experiments in order to compare the effects on abnormal eye morphogenesis.


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