ERK5 and CCL19 Regulate the Secondary Immune Response in Mice
| Autor: | Jaisel A Cervantes, Charlotte M Vines, Colin D Knight, Mika D Gehre, Colin A Bill |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 208:55.23-55.23 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.208.supp.55.23 |
| Popis: | C-C chemokine receptor 7 (CCR7) binds to its ligand CCL19, which is expressed on the surface of activated dendritic cells, antigen activated B-cells and within lymphoid organs. Previous studies showed that homozygous deletion of CCR7 or its ligands leads to increased production of antibodies. However, it is unclear to what extent CCL19 contributes to this phenotype, since stimulation of naïve T cells with the second CCR7 ligand, CCL21, is sufficient to promote trafficking of T cells to the lymph nodes. We hypothesized that using a CCR7 antagonist during immunization would create a pseudo CCR7(−) state. Previously, we have shown that signaling via CCR7/CCL19 is mediated through ERK5. Therefore, we investigated the effect of the CCL19 antagonist CCL198-83 or blocking downstream signaling through the CCR7/CCL19 axis by using ERK5flox/flox/Lck-CRE mice, on antibody production. We found in the presence of CCL198-83 mice generated significantly higher levels of IgG1, IgG2b, and IgG3 than control mice in response to vaccination with DNP-KLH. In addition, we found that the level of affinity maturation between the mice treated with CCL198-83 was not significantly different from control mice demonstrating that in the absence of CCL19 activity, affinity maturation can occur. To assess the role of ERK5 signaling pathway, we used ERK5flox/flox/Lck-CRE mice to examine the effect of CCR7 downstream signaling on antibody production. We found that these mice produced significantly higher levels of IgG1 and IgG3 following immunization with DNP-KLH than the ERK5flox/flox control mice suggesting that the ERK5 pathway, at least in part, mediates signaling from CCR7/CCL19. Supported by NIH-SC1GM111172 NIH-2U54MD007592 NSF-HRD-182675 NIH-5UL1GM118970 |
| Databáze: | OpenAIRE |
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