Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1

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

article

Kedeye Tuerxun¹  Kristine Midtbö¹  Eva Särndahl¹  Egor Vorontsov³  Roger Karlsson⁴  Alexander Persson¹  Robert Kruse¹  Daniel Eklund¹ 

[1] Faculty of Medicine and Health, School of Medical Sciences, Örebro University;Inflammatory Response and Infection Susceptibility Centre ,(iRiSC), Faculty of Medicine and Health, Örebro University;Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg;Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy of the University of Gothenburg;Department of Clinical Microbiology, Sahlgrenska University Hospital;Nanoxis Consulting AB;Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University

关键词: endotoxin tolerance;    immunosuppression;    inflammation;    MDSCs;    sepsis;   

DOI  :  10.1002/JLB.3A0421-216R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Myeloid-derived suppressor cells (MDSCs) are functionally immunosuppressive cellsthat arise and expand during extensive inflammatory conditions by increasedhematopoietic output or reprogramming of immune cells. In sepsis, an increase of circulating MDSCs is associated with adverse outcomes, but unique traits that can beused to identify increased activity of MDSCs are lacking. By using endotoxin tolerance as a model of sepsis-induced monocytic MDSCs (M-MDSC-like cells), this studyaims to identify the mediator and transcriptional regulator profile associated with MMDSC activity. After analyzing 180 inflammation-associated proteins, a profile of differentially expressed cytokines was found in M-MDSC-like cells versus normal monocytes stimulated with LPS. These cytokines were associated with 5 candidate transcription factors, where particularly PU.1 showed differential expression on both transcriptional and protein levels in M-MDSC-like cells. Furthermore, inhibition of PU.1led to increased production of CXCL5 and CCL8 in M-MDSC-like cells indicating itsrole in regulating the ability of M-MDSC-like cells to recruit other immune cells. Takentogether, the study identifies a unique profile in the pattern of immune mediatorsdefining M-MDSC activity upon LPS stimulation, which offers a functional link to theircontribution to immunosuppression.

【 授权许可】

CC BY