PMID- 33774873 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20210719 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 35 IP - 5 DP - 2021 May TI - Macrophage migration inhibitory factor promotes the migration of dendritic cells through CD74 and the activation of the Src/PI3K/myosin II pathway. PG - e21418 LID - 10.1096/fj.202001605R [doi] AB - Constitutively expressed by innate immune cells, the cytokine macrophage migration inhibitory factor (MIF) initiates host immune responses and drives pathogenic responses in infectious, inflammatory, and autoimmune diseases. Dendritic cells (DCs) express high levels of MIF, but the role of MIF in DC function remains poorly characterized. As migration is critical for DC immune surveillance, we investigated whether MIF promoted the migration of DCs. In classical transwell experiments, MIF(-/-) bone marrow-derived DCs (BMDCs) or MIF(+/+) BMDCs treated with ISO-1, an inhibitor of MIF, showed markedly reduced spontaneous migration and chemotaxis. CD74(-/-) BMDCs that are deficient in the ligand-binding component of the cognate MIF receptor exhibited a migration defect similar to that of MIF(-/-) BMDCs. Adoptive transfer experiments of LPS-matured MIF(+/+) and MIF(-/-) and of CD74(+/+) and CD74(-/-) BMDCs injected into the hind footpads of homologous or heterologous mice showed that the autocrine and paracrine MIF activity acting via CD74 contributed to the recruitment of DCs to the draining lymph nodes. Mechanistically, MIF activated the Src/PI3K signaling pathway and myosin II complexes, which were required for the migration of BMDCs. Altogether, these data show that the cytokine MIF exerts chemokine-like activity for DC motility and trafficking. CI - (c) 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. FAU - Ives, Annette AU - Ives A AD - Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. FAU - Le Roy, Didier AU - Le Roy D AD - Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. FAU - Theroude, Charlotte AU - Theroude C AD - Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. FAU - Bernhagen, Jurgen AU - Bernhagen J AUID- ORCID: 0000-0003-2996-2652 AD - Chair of Vascular Biology, Institute for Stroke and Dementia Research (ISD), Klinikum der Universitat Munchen (KUM), Ludwig-Maximilians-University (LMU), Munich, Germany. AD - Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. FAU - Roger, Thierry AU - Roger T AUID- ORCID: 0000-0002-9358-0109 AD - Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. FAU - Calandra, Thierry AU - Calandra T AUID- ORCID: 0000-0003-3051-1285 AD - Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (Chemokines) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Macrophage Migration-Inhibitory Factors) RN - 0 (invariant chain) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 3.6.1.- (Myosin Type II) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - EC 5.3.2.1 (Mif protein, mouse) SB - IM MH - Animals MH - Antigens, Differentiation, B-Lymphocyte/*physiology MH - Cells, Cultured MH - Chemokines/metabolism MH - *Chemotaxis MH - Dendritic Cells/cytology/*physiology MH - Histocompatibility Antigens Class II/*physiology MH - Immunity MH - Intramolecular Oxidoreductases/genetics/*metabolism MH - Macrophage Migration-Inhibitory Factors/genetics/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myosin Type II/genetics/*metabolism MH - Phosphatidylinositol 3-Kinases/genetics/*metabolism MH - Signal Transduction MH - src-Family Kinases/genetics/*metabolism OTO - NOTNLM OT - MIF OT - chemokine OT - cytokine OT - dendritic cell OT - innate immunity OT - motility EDAT- 2021/03/29 06:00 MHDA- 2021/07/20 06:00 CRDT- 2021/03/28 21:14 PHST- 2021/01/14 00:00 [revised] PHST- 2020/06/26 00:00 [received] PHST- 2021/01/21 00:00 [accepted] PHST- 2021/03/28 21:14 [entrez] PHST- 2021/03/29 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] AID - 10.1096/fj.202001605R [doi] PST - ppublish SO - FASEB J. 2021 May;35(5):e21418. doi: 10.1096/fj.202001605R.