TY - JOUR
T1 - Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells
AU - Rudloff, Ina
AU - Cho, Steven X.
AU - Lao, Jason C.
AU - Ngo, Devi
AU - McKenzie, Matthew
AU - Nold-Petry, Claudia A.
AU - Nold, Marcel F.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85017319001&partnerID=8YFLogxK
U2 - 10.1189/jlb.3MA0616-287R
DO - 10.1189/jlb.3MA0616-287R
M3 - Article
AN - SCOPUS:85017319001
VL - 101
SP - 901
EP - 911
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 4
ER -