Constitutive Expression of CCL22 Is Mediated by T Cell-Derived GM-CSF
| Autor: | Konstantin Schnell, Stefan Endres, Bastian Meyer, Patrick Layritz, David Anz, Viola Vetter, Maximilian Martin Ludwig Knott, Juliane Gruen, Ignazio Piseddu, Benjamin Kühnemuth, Carolin Perleberg, Natascha Röhrle, Gabriela M. Wiedemann, Stefan Moder, Stephan Eiber, Moritz Rapp |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adoptive cell transfer
medicine.medical_treatment T cell Immunology CD11c Inflammation Biology T-Lymphocytes Regulatory Recombination-activating gene Gonadotropin-Releasing Hormone 03 medical and health sciences 0302 clinical medicine Immune system Th2 Cells medicine Immunology and Allergy Animals Chemokine CCL22 Mice Knockout CD11 Antigens Granulocyte-Macrophage Colony-Stimulating Factor Dendritic Cells Cell biology Lymphatic system Cytokine medicine.anatomical_structure Gene Expression Regulation medicine.symptom 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 205(8) |
| ISSN: | 1550-6606 |
| Popis: | CCL22 is a key mediator of leukocyte trafficking in inflammatory immune responses, allergy, and cancer. It acts by attracting regulatory T cells and Th2 cells via their receptor CCR type 4 (CCR4). Beyond its role in inflammation, CCL22 is constitutively expressed at high levels in lymphoid organs during homeostasis, where it controls immunity by recruiting regulatory T cells to dendritic cells (DCs). In this study, we aimed to identify the mechanisms responsible for constitutive CCL22 expression. We confirmed that CD11c+ DCs are the exclusive producers of CCL22 in secondary lymphatic organs during homeostasis. We show that in vitro both murine splenocytes and human PBMCs secrete CCL22 spontaneously without any further stimulation. Interestingly, isolated DCs alone, however, are unable to produce CCL22, but instead require T cell help. In vitro, only the coculture of DCs with T cells or their supernatants resulted in CCL22 secretion, and we identified T cell–derived GM-CSF as the major inducer of DC-derived CCL22 expression. In vivo, Rag1−/− mice, which lack functional T cells, have low CCL22 levels in lymphoid organs, and this can be restored by adoptive transfer of wild-type T cells or administration of GM-CSF. Taken together, we uncover T cell–derived GM-CSF as a key inducer of the chemokine CCL22 and thus, to our knowledge, identify a novel role for this cytokine as a central regulator of immunity in lymphatic organs. This knowledge could contribute to the development of new therapeutic interventions in cancer and autoimmunity. |
| Databáze: | OpenAIRE |
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