Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells.

Autor: Rudloff I; Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., Cho SX; Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., Lao JC; Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., Ngo D; Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., McKenzie M; Centre for Genetic Diseases, Hudson Institute of Medical Research, Melbourne, Victoria, Australia; and.; Department of Molecular and Translational Science, Monash University, Melbourne, Victoria, Australia., Nold-Petry CA; Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., Nold MF; Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia; marcel.nold@monash.edu.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2017 Apr; Vol. 101 (4), pp. 901-911. Date of Electronic Publication: 2016 Nov 23.
DOI: 10.1189/jlb.3MA0616-287R
Abstrakt: The interleukin (IL)-1 family member IL-37 is one of few anti-inflammatory cytokines, and it is capable of countering a broad spectrum of proinflammatory assaults. Although it is known that leukocytes are a major source of IL-37, knowledge on IL-37 production and secretion in specific immune cell types remains limited. Thus, we investigated IL-37 mRNA expression as well as protein production and secretion in human PBMCs. In PBMCs stimulated with agonists of Toll-like receptors (TLRs) 1-6 and 9, IL1F7 (the IL-37-encoding gene) was induced up to 9-fold, peaked at 6-8 h and returned to steady-state at 72 h. LPS-induced IL1F7 expression comprised isoforms b and c but not a and e Flow cytometry revealed that among IL-37 + PBMCs, monocytes predominated (81-91%), but T cells (6-8%) and myeloid dendritic cells (mDCs, 1-2%) also contributed to the IL-37 + leukocyte pool. Monocytes and mDCs, but not T cells, were capable of secreting IL-37. Whereas monocytes and mDCs secreted IL-37 upon LPS stimulation, only mDCs also released IL-37 at steady-state. Among monocyte subsets, IL-37 was LPS inducible and secreted only in classical and, although less pronounced, in intermediate monocytes; secretion was observed as early as 3 h after stimulation. Overall, our data suggest that constitutive IL-37 secretion by mDCs may serve to maintain an anti-inflammatory milieu at steady state, whereas IL-37 is stored in monocytes to be available for rapid release upon inflammatory encounters, thus acting as a novel anti-inflammatory alarmin. These insights may prove important to advancing towards clinical use the protective functions of one of the most powerful anti-inflammatory mediators so far discovered.
(© Society for Leukocyte Biology.)
Databáze: MEDLINE
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