PMID- 32557554 OWN - NLM STAT- MEDLINE DCOM- 20210201 LR - 20210201 IS - 1521-4141 (Electronic) IS - 0014-2980 (Linking) VI - 50 IP - 11 DP - 2020 Nov TI - A two-step human culture system replicates intestinal monocyte maturation cascade: Conversion of tissue-like inflammatory monocytes into macrophages. PG - 1676-1690 LID - 10.1002/eji.202048555 [doi] AB - Monocyte maturation program into macrophages (MPhi) is well defined in murine gut under homeostatic or inflammatory conditions. Obviously, in vivo tracking of monocytes in inflamed tissues remains difficult in humans. Furthermore, in vitro models fall short in generating the surrogates of transient extravasated tissue inflammatory monocytes. Here, we aimed to unravel environmental cues that replicated the human monocyte "waterfall" process in vitro by first, generating tissue-like inflammatory monocytes, which were then shifted toward MPhi. Purified CD14(+) CD16(-) monocytes, cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma and IL23, differentiated into CD14(+) CD163(-) cells that displayed a monocyte-like morphology. In vitro generated inflammatory CD14(+) CD163(-) (inflammatory monocyte-like cells) cells promoted IL-1beta-dependent memory Th17 and Th17/Th1 responses, like the CD14(+) CD163(-) mo-like cells that accumulate in inflamed colon of Crohn's disease patients. Next, in vitro generated inflammatory monocyte-like cells converted to functional CD163(+) MPhi following exposure to TGF-beta and IL10. Gene set enrichment analysis further revealed a shared molecular signature between converted CD163(+) MPhi and MPhi detected in various inflamed nonlymphoid and lymphoid diseased tissues. Our findings propose a two-step in vitro culture that recapitulates human monocyte maturation cascade in inflamed tissue. Manipulation of this process might open therapeutic avenues for chronic inflammatory disorders. CI - (c) 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Bsat, Marwa AU - Bsat M AD - Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada. FAU - Chapuy, Laurence AU - Chapuy L AD - Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada. FAU - Rubio, Manuel AU - Rubio M AD - Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada. FAU - Sarfati, Marika AU - Sarfati M AUID- ORCID: 0000-0003-2318-0713 AD - Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada. LA - eng GR - MOP#130533/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200629 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD163 antigen) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Receptors, Cell Surface) RN - 0 (Transforming Growth Factor beta) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Antigens, Differentiation, Myelomonocytic/metabolism MH - Cell Differentiation/physiology MH - Cells, Cultured MH - Coculture Techniques/methods MH - Colon/cytology/metabolism MH - Humans MH - Inflammation/metabolism/*pathology MH - Interleukin-10/metabolism MH - Lipopolysaccharide Receptors/metabolism MH - Macrophages/*cytology/metabolism MH - Mice MH - Monocytes/*cytology/metabolism MH - Receptors, Cell Surface/metabolism MH - Th1 Cells/cytology/metabolism MH - Th17 Cells/cytology/metabolism MH - Transforming Growth Factor beta/metabolism OTO - NOTNLM OT - Crohn's disease OT - IL10 OT - IL23 OT - Macrophages OT - TGF-beta EDAT- 2020/06/20 06:00 MHDA- 2021/02/02 06:00 CRDT- 2020/06/20 06:00 PHST- 2020/01/17 00:00 [received] PHST- 2020/05/05 00:00 [revised] PHST- 2020/06/17 00:00 [accepted] PHST- 2020/06/20 06:00 [pubmed] PHST- 2021/02/02 06:00 [medline] PHST- 2020/06/20 06:00 [entrez] AID - 10.1002/eji.202048555 [doi] PST - ppublish SO - Eur J Immunol. 2020 Nov;50(11):1676-1690. doi: 10.1002/eji.202048555. Epub 2020 Jun 29.