Zbtb10 transcription factor is crucial for murine cDC1 activation and cytokine secretion

Details

Serval ID
serval:BIB_40DDE80854B5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Zbtb10 transcription factor is crucial for murine cDC1 activation and cytokine secretion
Journal
European Journal of Immunology
Author(s)
Smita Shuchi, Ghosh Arup, Biswas Viplov Kumar, Ahad Abdul, Podder Sreeparna, Jha Atimukta, Sen Kaushik, Acha-Orbea Hans, Raghav Sunil K.
ISSN
0014-2980
1521-4141
ISSN-L
0014-2980
Publication state
Published
Issued date
05/2021
Peer-reviewed
Oui
Volume
51
Number
5
Pages
1126-1142
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Dendritic cell (DC) activation and cytokine production is tightly regulated. In this study, we found that Zbtb10 expression is activation dependent and it is essential for the immunogenic function of cDC1. Zbtb10 knockdown (KD) significantly reduced the expression of co-stimulatory genes CD80 and CD86 along with cytokines including IL-12, IL-6, and IL-10, in activated cDC1 Mutu-DC line. Consequently, the clonal expansion of CD44 <sup>+</sup> effector T cells in co-cultured CD4 <sup>+</sup> T cells was drastically reduced owing to significantly reduced IL-2. At the same time, these CD44 <sup>+</sup> effector T cells were unable to differentiate toward Tbet <sup>+</sup> IFNγ <sup>+</sup> Th1 subtype. Instead, an increased frequency of Th2 cells expressing GATA3 <sup>+</sup> and IL-13 <sup>+</sup> was observed. Interestingly, in Zbtb10 KD condition the co-cultured T cells depicted increased expression of PD1 and LAG3, the T-cell anergic markers. Moreover, the global transcriptome analysis identified that Zbtb10 is pertinent for DC activation and its depletion in cDC1 completely shuts down their immune responses. Mechanistic analysis revealed that Zbtb10 KD enhanced the expression of NKRF (NF-κB repressing factor) leading to drastic suppression of NF-κB related genes. Zbtb10 KD abrogated p65 and RelB nuclear translocation, thereby controlling the activation and maturation of cDC1 and the ensuing adaptive T cell responses.
Keywords
Immunology, Immunology and Allergy
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2021 13:31
Last modification date
08/07/2021 5:37
Usage data