Protein kinase CK2 controls T-cell polarization through dendritic cell activation in response to contact sensitizers

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Pallardy, Marc¹  Rousseau, Philippe¹  Cochet, Claude²  ne⁴  Damiens, Marie-Hé⁵  Kerdine-Rö⁵  El Ali, Zeina⁶  Chollet-Martin, Sylvie⁶  Gallais, Yann⁷  Filhol, Odile⁷  mer, Saadia⁸  lè⁸ 

[1] Paris‐and;Cancer and Infection Biology, UMR1036, INSERM, Institute of Life Sciences Research and Technology (iRTSV), Atomic Energy and Alternative Energy Commission (CEA), Grenoble, France;Malabry, France;Saclay, ChâSud, UniversitéUMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris‐tenay‐

关键词: dendritic cell;    protein kinase;    Th1/Th2/Th17 cell;    allergic contact dermatitis;    cytokine;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin disease caused by chemicals present in the daily or professional environment. NiSO₄ and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These contact sensitizers are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs; professional APCs), leading to the generation of CD8⁺ Tc1/Tc17 and CD4⁺ Th1/Th17 effector T cells. In the present study, using a peptide array approach, we identified protein kinase CK2 as a novel kinase involved in the activation of human monocyte-derived DCs (MoDCs) in response to NiSO₄ and DNCB. Inhibition of CK2 activity in MoDCs led to an altered mature phenotype with lower expression of CD54, PDL-1, CD86, and CD40 in response to NiSO₄ or DNCB. CK2 activity also regulated proinflammatory cytokine production, such as TNF-α, IL-1β, and IL-23 in MoDCs. Moreover, in a DC/T cell coculture model in an allogeneic setup, CK2 activity in MoDCs played a major role in Th1 polarization in response to NiSO₄ and DNCB. CK2 inhibition in MoDCs led to an enhanced Th2 polarization in the absence of contact sensitizer stimulation.

【 授权许可】

CC BY