Back

Essential role of an acidic endosomal environment in JAK3-mediated signal transduction

Amano, Y.; Tanaka, N.; Takeshita, T.; Kojima, K.

2023-09-12 immunology
10.1101/2023.09.07.556780 bioRxiv
Show abstract

The endosome, an acidic organelle, is a platform for endocytic trafficking and signal transduction. Chloroquine, an intercellular acidic vesicle neutralizer (IAVN), has been used to treat autoimmune diseases. Its immunosuppressive mechanism remains unclear, although several modes of action attributable to lysosomal dysfunction have been postulated. This study found that IAVNs, including chloroquine, can selectively interfere with common cytokine receptor {gamma} chain ({gamma}c) cytokine-induced signal transduction. Our data show that JAK3 targets endosomal membranes in an acidic pH-dependent manner, which is essential for {gamma}c-cytokine-induced functional signal complex formation and signal activation. Among IAVNs, Monensin and similar ionophores were particularly effective in suppressing {gamma}c-cytokine-induced cell proliferation in vitro. Monensin exerted therapeutic effects in a collagen-induced arthritis mouse model by interfering with T helper 17 cells. Our findings help further understand the immunosuppressive mechanism of IAVNs and unveil the spatial regulation of JAK3-mediated signal transduction via endosomes.

Matching journals

The top 8 journals account for 50% of the predicted probability mass.

1
Cell Reports
○ 1498 papers in training set
Top 0.9%
12.6%
Similar papers in this journal
2
Nature Communications
○ 5641 papers in training set
Top 16%
11.8%
Similar papers in this journal
3
eLife
● 5828 papers in training set
Top 20%
6.2%
Similar papers in this journal
4
Scientific Reports
○ 3612 papers in training set
Top 16%
5.5%
Similar papers in this journal
5
Frontiers in Immunology
○ 638 papers in training set
Top 3%
4.0%
Similar papers in this journal
6
Signal Transduction and Targeted Therapy
○ 30 papers in training set
Top 0.1%
3.5%
7
Science Signaling
● 65 papers in training set
Top 0.2%
3.2%
8
iScience
○ 1154 papers in training set
Top 7%
3.2%
50% of probability mass above
9
Cell Death & Disease
147 papers in training set
Top 1%
2.4%
10
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 21%
2.4%
11
Cellular and Molecular Life Sciences
○ 96 papers in training set
Top 0.4%
2.4%
12
Cell Communication and Signaling
○ 51 papers in training set
Top 0.2%
2.4%
13
Nature Immunology
○ 79 papers in training set
Top 1%
2.4%
14
Cell Chemical Biology
○ 94 papers in training set
Top 0.5%
2.4%
15
Acta Pharmaceutica Sinica B
○ 11 papers in training set
Top 0.1%
2.4%
16
EMBO Reports
○ 263 papers in training set
Top 3%
2.0%
17
Communications Biology
○ 993 papers in training set
Top 12%
1.9%
18
Journal of Biological Chemistry
○ 690 papers in training set
Top 6%
1.7%
19
The Journal of Immunology
◐ 166 papers in training set
Top 2%
1.5%
20
Life Science Alliance
● 285 papers in training set
Top 5%
1.3%
21
Science Advances
● 1243 papers in training set
Top 23%
1.3%
22
Cellular & Molecular Immunology
○ 14 papers in training set
Top 0.1%
1.1%
23
Autophagy
○ 39 papers in training set
Top 0.4%
1.0%
24
Advanced Science
○ 286 papers in training set
Top 8%
1.0%
25
European Journal of Immunology
○ 60 papers in training set
Top 1%
0.9%
26
mBio
● 833 papers in training set
Top 11%
0.8%
27
ACS Chemical Biology
● 167 papers in training set
Top 3%
0.8%
28
PLOS Pathogens
● 820 papers in training set
Top 9%
0.8%
29
Allergy
○ 25 papers in training set
Top 0.5%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.