In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 147.16-147.16
Kurzfassung:
Mast cells are innate immune cells derived from hematopoietic stem cells. Mechanisms controlling IL-3-directed mast cell differentiation are incompletely defined. MAPK contributes to IL-3R-mediated signaling, yet specific contributions to maturation of functional mast cells are undetermined. We aimed to evaluate the role of the MAPK signaling nodes—JNK, ERK, and p38—in mast cell differentiation, and explore contributions to epigenetic modifier expression. Bone marrow-derived mast cell (BMMC) cultures were established from C57BL/6 mice and differentiated for 7 weeks in the presence or absence of MAPK inhibitors (JNK, JNK-IN-8; ERK, SCH772984; p38, GW856553X). Following inhibitor withdrawal (5 days), phenotypic and functional characteristics of IgE-sensitized BMMCs were assessed using flow cytometry, ELISA, and β-hexosaminidase release assays. Cells differentiated under JNK inhibition showed a significant impairment in the secretion of IL-6 (p & lt;0.05) and IL-13 (p & lt;0.05) and a non-significant impairment in TNF and CCL1 24 hrs post allergen challenge. Degranulation was also significantly decreased (by 25%, p & lt;0.05) in JNK-inhibitor-cultured BMMCs. Expression of c-kit and level of sensitization by IgE was unaffected by impaired JNK signaling. Treatment with p38 and ERK inhibitors did not affect receptor expression, cytokine secretion, or degranulation. Interrogation of MAPK-dependent modifiers of histone acetylation by qPCR and western blot showed that JNK-mediated contributions to mast cell functional responses were independent of HDACs and HATs examined. These results position JNK as a critical contributor to normal mast cell differentiation and potential target in modulating mast cell phenotype.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.147.16
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2020
ZDB Id:
1475085-5
