Progesterone decreased indoleamine 2,3-dioxygenase 1(IDO1) expression in early pregnancy chorionic villi and decidua

Autoimmunity ◽  
2021 ◽  
pp. 1-7
Author(s):  
Minyan Yang ◽  
Guanyou Huang ◽  
Hua Qian ◽  
Jun Wang ◽  
Shuyun Zhao ◽  
...  
2012 ◽  
Vol 303 (2) ◽  
pp. R135-R143 ◽  
Author(s):  
Isabelle Wolowczuk ◽  
Benjamin Hennart ◽  
Audrey Leloire ◽  
Alban Bessede ◽  
Marion Soichot ◽  
...  

Human obesity is characterized by chronic low-grade inflammation in white adipose tissue and is often associated with hypertension. The potential induction of indoleamine 2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme in tryptophan/kynurenine degradation pathway, by proinflammatory cytokines, could be associated with these disorders but has remained unexplored in obesity. Using immunohistochemistry, we detected IDO1 expression in white adipose tissue of obese patients, and we focused on its contribution in the regulation of vascular tone and on its immunoregulatory effects. Concentrations of tryptophan and kynurenine were measured in sera of 36 obese and 15 lean women. The expression of IDO1 in corresponding omental and subcutaneous adipose tissues and liver was evaluated. Proinflammatory markers and T-cell subsets were analyzed in adipose tissue via the expression of CD14, IL-18, CD68, TNFα, CD3ε, FOXP3 [a regulatory T-cell (Treg) marker] and RORC (a Th17 marker). In obese subjects, the ratio of kynurenine to tryptophan, which reflects IDO1 activation, is higher than in lean subjects. Furthermore, IDO1 expression in both adipose tissues and liver is increased and is inversely correlated with arterial blood pressure. Inflammation is associated with a T-cell infiltration in obese adipose tissue, with predominance of Th17 in the omental compartment and of Treg in the subcutaneous depot. The Th17/Treg balance is decreased in subcutaneous fat and correlates with IDO1 activation. In contrast, in the omental compartment, despite IDO1 activation, the Th17/Treg balance control is impaired. Taken together, our results suggest that IDO1 activation represents a local compensatory mechanism to limit obesity-induced inflammation and hypertension.


1995 ◽  
Vol 7 (6) ◽  
pp. 1539 ◽  
Author(s):  
M Jaggi ◽  
PK Mehrotra ◽  
SC Maitra ◽  
SL Agarwal ◽  
K Das ◽  
...  

Two cell types, the cyto- and syncytio-trophoblasts, were identified in human chorionic villi of 6-10 weeks' gestation. The intracellular organization of these cells was examined. Ultrathin sections of small pieces of chorionic villi revealed the presence of a multinucleate syncytiotrophoblastic layer, whose surface was covered with microvilli. The cytotrophoblasts, however, had a single large nucleus with a prominent nucleolus. An interesting feature of the basement membrane of these cells was the presence of aggregates of dark granules in samples of the earlier gestational age (6-8 weeks) and granular bodies having a dense outer ring and a translucent inner ring with a lucid central area in samples of 8-10 weeks' gestation. Both types of granules are mineralized and are assumed to perform a buffering role for maintaining the neutrality of the layer.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3043-3043 ◽  
Author(s):  
Alton Hiscox ◽  
Heather Gustafson ◽  
Joseph Couto ◽  
Zhiming Liao ◽  
Yifei Zhu ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Yvonne Grobben ◽  
Jos de Man ◽  
Antoon M. van Doornmalen ◽  
Michelle Muller ◽  
Nicole Willemsen-Seegers ◽  
...  

Indoleamine 2,3-dioxygenase (IDO1) is a key regulator of immune suppression by catalyzing the oxidation of L-tryptophan. IDO1 expression has been related to poor prognosis in several cancers and to resistance to checkpoint immunotherapies. We describe the characterization of a novel small molecule IDO1 inhibitor, NTRC 3883-0, in a panel of biochemical and cell-based assays, and various cancer models. NTRC 3883-0 released the inhibitory effect of IDO1 on CD8-positive T cell proliferation in co-cultures of IDO1-overexpressing cells with healthy donor lymphocytes, demonstrating its immune modulatory activity. In a syngeneic mouse model using IDO1-overexpressing B16F10 melanoma cells, NTRC 3883-0 effectively counteracted the IDO1-induced modulation of L-tryptophan and L-kynurenine levels, demonstrating its in vivo target modulation. Finally, we studied the expression and activity of IDO1 in primary cell cultures established from the malignant ascites of ovarian cancer patients. In these cultures, IDO1 expression was induced upon stimulation with IFNγ, and its activity could be inhibited by NTRC 3883-0. Based on these results, we propose the use of ascites cell-based functional assays for future patient stratification. Our results are discussed in light of the recent discontinuation of clinical trials of more advanced IDO1 inhibitors and the reconsideration of IDO1 as a valid drug target.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
I-Chien Chen ◽  
Kuen-Haur Lee ◽  
Ying-Hua Hsu ◽  
Wei-Ran Wang ◽  
Chuan-Mu Chen ◽  
...  

Aims. Cancer cells use the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to suppress the host’s immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. Higher IDO1 expression was shown to be involved in colorectal cancer (CRC) progression and to be correlated with impaired clinical outcome. However, the potential correlation between the expression of IDO1 in a CRC population with a low mutation rate of theAPCgene remains unknown.Material and Methods. Tissues and blood samples were collected from 192 CRC patients. The expressions of IDO1, tryptophan 2,3-dioxygenase (TDO2), and beta-catenin proteins were analyzed by immunohistochemistry. Microsatellite instability (MSI) was determined by PCR amplification of microsatellite loci.Results. The results showed that high IDO1 or TDO2 protein expression was associated with characteristics of more aggressive phenotypes of CRC. For the first time, they also revealed a positive correlation between the abnormal expression of beta-catenin and IDO1 or TDO2 proteins in a CRC population with a low mutation rate ofAPC.Conclusion. We concluded that an IDO1-regulated molecular pathway led to abnormal expression of beta-catenin in the nucleus/cytoplasm of CRC patients with low mutation rate ofAPC, making IDO1 an interesting target for immunotherapy in CRC.


2019 ◽  
Vol 54 (S1) ◽  
pp. 14-14
Author(s):  
L. Benitez Quintanilla ◽  
M. Pauta ◽  
A. Soler ◽  
L. Rodriguez‐Revenga ◽  
M. Grande ◽  
...  

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