IL-33 promotes type 1 cytokine expression via p38 MAPK in human NK cells
| Autor: | David E. Ochayon, Ayad Ali, Leah C. Kottyan, Stephen N. Waggoner, Durga Krishnamurthy, Pablo C. Alarcon, Michael T. Borchers |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.medical_treatment p38 mitogen-activated protein kinases Immunology ADAM17 Protein Biology p38 Mitogen-Activated Protein Kinases Article Cell Line Interferon-gamma 03 medical and health sciences 0302 clinical medicine medicine Humans Immunology and Allergy Secretion RNA Messenger Phosphorylation Tumor Necrosis Factor-alpha Innate lymphoid cell Cell Biology STAT4 Transcription Factor Interleukin-33 Interleukin-1 Receptor-Like 1 Protein Interleukin-12 Cell biology Killer Cells Natural Interleukin 33 030104 developmental biology Cytokine Interleukin 12 Cytokines Tumor necrosis factor alpha 030215 immunology |
| Zdroj: | J Leukoc Biol |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1002/jlb.3a0120-379rr |
| Popis: | This study tests the hypothesis that activation of MAPK by physiologically relevant concentrations of IL-33 contributes to enhanced cytokine expression by IL-12 stimulated human NK cells. While IL-33 canonically triggers type 2 cytokine responses, this cytokine can also synergize with type 1 cytokines like IL-12 to provoke IFN-γ. We show that picogram concentrations of IL-12 and IL-33 are sufficient to promote robust secretion of IFN-γ by human NK cells that greatly exceeds resposes to either cytokine alone. Nanogram doses of IL-33, potentially consistent with levels in tissue microenvironments, synergize with IL-12 to induce secretion of additional cytokines, including TNF and GM-CSF. IL-33-induced activation of the p38 MAPK pathway in human NK cells is crucial for enhanced release of IFN-γ and TNF in response to IL-12. Mechanistically, IL-33-induced p38 MAPK signaling enhances stability of IFNG transcripts and triggers A disintegrin and metalloproteinase domain 17 (ADAM17) mediated cleavage of TNF from the cell surface. These data support our hypothesis and suggest that altered sensitivity of NK cells to IL-12 in the presence of IL-33 may have important consequences in diseases associated with mixed cytokine milieus, like asthma and chronic obstructive pulmonary disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text