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Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Apr 29; Vol. 81 (1), pp. 199. Date of Electronic Publication: 2024 Apr 29. - Publication Year :
- 2024
-
Abstract
- Tyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2-deficient (Tyk2 <superscript>-/-</superscript> ) mice. Splenic B cell subpopulations were altered in Tyk2 <superscript>-/-</superscript> compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged. Likewise, there was an imbalance in transitional B cells in juvenile Tyk2 <superscript>-/-</superscript> mice. RNA sequencing analysis of adult MZ and FO cells isolated from Tyk2 <superscript>-/-</superscript> and WT mice in homeostasis revealed altered expression of IFN-I and Toll-like receptor 7 (TLR7) signaling pathway genes. Flow cytometry assays corroborated a lower expression of TLR7 in MZ B cells from Tyk2 <superscript>-/-</superscript> mice. Splenic B cell cultures showed reduced proliferation and differentiation responses after activation with TLR7 ligands in Tyk2 <superscript>-/-</superscript> compared to WT mice, with a similar response to lipopolysaccharide (LPS) or anti-CD40 + IL-4. IgM, IgG, IL-10 and IL-6 secretion was also decreased in Tyk2 <superscript>-/-</superscript> B cell cultures. This reduced response of the TLR7 pathway in Tyk2 <superscript>-/-</superscript> mice was partially restored by IFNα addition. In conclusion, there is a crosstalk between TYK2 and TLR7 mediated by an IFN-I feedback loop, which contributes to the establishment of MZ B cells and to B cell proliferation and differentiation.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Cell Differentiation
Cell Proliferation
Cells, Cultured
Membrane Glycoproteins metabolism
Membrane Glycoproteins genetics
Mice, Inbred C57BL
Mice, Knockout
B-Lymphocytes metabolism
B-Lymphocytes immunology
Interferon Type I metabolism
Signal Transduction
Spleen cytology
Spleen metabolism
Toll-Like Receptor 7 metabolism
Toll-Like Receptor 7 genetics
TYK2 Kinase metabolism
TYK2 Kinase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 81
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 38683377
- Full Text :
- https://doi.org/10.1007/s00018-024-05234-y