Back to Search
Start Over
The ASCIZ-DYNLL1 Axis Is Essential for TLR4-Mediated Antibody Responses and NF-κB Pathway Activation.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2021 Nov 22; Vol. 41 (12), pp. e0025121. Date of Electronic Publication: 2021 Sep 20. - Publication Year :
- 2021
-
Abstract
- Toll-like receptors (TLRs) and interleukin-1 (IL-1) receptors regulate immune and inflammatory responses by activating the NF-κB pathway. Here, we report that B-cell-specific loss of dynein light chain 1 (DYNLL1, LC8) or its designated transcription factor ASCIZ (ATMIN) leads to severely reduced in vivo antibody responses to TLR4-dependent but not T-cell-dependent antigens in mice. This defect was independent of DYNLL1's established roles in modulating BIM-dependent apoptosis and 53BP1-dependent antibody class-switch recombination. In B cells and fibroblasts, the ASCIZ-DYNLL1 axis was required for TLR4-, IL-1-, and CD40-mediated NF-κB pathway activation but dispensable for antigen receptor and tumor necrosis factor α (TNF-α) signaling. In contrast to previous reports that overexpressed DYNLL1 directly inhibits the phosphorylation and degradation of the NF-κB inhibitor IκBα, we found here that under physiological conditions, DYNLL1 is required for signal-specific activation of the NF-κB pathway upstream of IκBα. Our data identify DYNLL1 as a signal-specific regulator of the NF-κB pathway and indicate that it may act as a universal modulator of TLR4 (and IL-1) signaling with wide-ranging roles in inflammation and immunity.
- Subjects :
- Animals
B-Lymphocytes immunology
CD40 Antigens metabolism
Cells, Cultured
Cytoplasmic Dyneins genetics
Immunoglobulin Class Switching immunology
Mice
Mice, Inbred C57BL
NF-KappaB Inhibitor alpha metabolism
T-Lymphocytes immunology
Transcription Factors genetics
Tumor Necrosis Factor-alpha metabolism
Tumor Suppressor p53-Binding Protein 1 immunology
Antibody Formation immunology
Cytoplasmic Dyneins metabolism
NF-kappa B metabolism
Toll-Like Receptor 4 immunology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 41
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 34543116
- Full Text :
- https://doi.org/10.1128/MCB.00251-21