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The soluble cytoplasmic tail of CD45 regulates T‐cell activation via TLR4 signaling
- Source :
- European Journal of Immunology. 51:3176-3185
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- The soluble cytoplasmic tail of CD45 (ct-CD45) is a cleavage fragment of CD45, that is generated during the activation of human phagocytes. Upon release to the extracellular space, ct-CD45 binds to human T cells and inhibits their activation in vitro. Here, we studied the potential role of TLR4 as a receptor for ct-CD45. Treatment of Jurkat TLR4/CD14 reporter cells with ct-CD45 induced the upregulation of the reporter gene NFκB-eGFP and could be blocked by inhibitors of TLR4 signaling. Conversely, ct-CD45 did not promote the NFκB-controlled eGFP induction in reporter cells expressing TLR1, TLR2, and TLR6 transgenes and did not lead to the activation of the transcription factors NFκB, AP-1, and NFAT in a Jurkat reporter cell line expressing endogenous TLR5. Moreover, ct-CD45 binds to recombinant TLR4 in an in vitro assay and this association was reduced in the presence of oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine. Blockade of TLR4 with mAb HTA125 partially reversed the ct-CD45-mediated inhibition of T-cell proliferation. Interestingly, targeting of TLR4 with mAb W7C11 also suppressed T-cell proliferation. In summary, the results of this study demonstrate that ct-CD45 acts via a noncanonical TLR4 activation pathway on T cells, which modulates TCR signaling.
- Subjects :
- Reporter gene
T-Lymphocytes
T cell
Immunology
NFAT
Biology
Lymphocyte Activation
Jurkat cells
Cell biology
Toll-Like Receptor 4
Jurkat Cells
TLR2
medicine.anatomical_structure
Downregulation and upregulation
Cell culture
medicine
Humans
Leukocyte Common Antigens
Immunology and Allergy
Transcription factor
Cell Proliferation
Signal Transduction
Subjects
Details
- ISSN :
- 15214141 and 00142980
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi.dedup.....c985a03b0c508a5e13e52375bdd48177