Fig. 1

Reprogramming of monocytes into anti-inflammatory cells to regulate inflammation and adaptive immunity. a IL-1 β-induced reprogramming of monocytes: upon encounter with PAMPs (pattern-associated molecular patterns) or DAMPs (danger-associated molecular patterns), so-called PRRs (pattern recognition receptors), here TLR (toll-like receptor) transmits signals into the cell that activate caspase-1. Active caspase-1 cleaves immature pro-IL-1 β into mature IL-1 β which then is released into the environment to induce inflammation. In balanced redox homestasis, prolonged activation of monocytes leads to more increased production of counterbalancing IL-1RA (IL-1 receptor antagonist) and upregulation of IL-1 decoy receptor CD121b (IL-1R-type II). Both bind and neutralize pro-inflammatory IL-1 β and contribute to the resolution phase of the inflammatory response. b Glucocorticoid-stimulated monocytes (GCsM): GCs (glucocorticoids) are sensed by GC receptors and induce reprogramming of monocytes to anti-inflammatory cells. Upregulation of IL-1 decoy receptor CD121b is one hallmark of GCsM. In contact with adaptive immunity, here T cells, GCsM efficiently downregulate T cell activation through yet unidentified mechanisms. In vivo, in a model of T cell-induced colitis, this leads to complete remission of inflammatory tissue damage [13]. c GM-CSF-activated monocytes (GMaM): GM-CSF is bound by the GM-CSF receptor CD116 on monocytes. Likewise, also GM-CSF reprograms monocytes into anti-inflammatory cells but with different features to confer regulation of inflammatory response. While upregulation of CD121 is similar to GCsM, increased expression of the exo-enzymes CD39 and CD73 is unique to GMaM. Using active CD39 and CD73 GMaM are capable to breakdown extracellular ATP into AMP and subsequently to adensoine that is known to help differentiation of Tregs. In contact with naive T cells, this allows GMaM to induce the differentiation and expansion of of Foxp3⁺ Tregs. Therapeutical use of GMaM in a mouse model of colitis showed complete suppression of inflammation in vivo, presumably through induced Tregs [15, 16]