title: Lysophosphatidic acid converts monocytes into macrophages in both mice and humans.
abstract: Monocytes and macrophages represent critical arms of the innate immune system and are considered regulators and effectors of inflammation and the innate immune response. Monocytes can mobilize from bone marrow, traffic to their required destination, and differentiate into effector cells, depending on the local tissue environment, to perform multiple roles during infection or inflammation, making them important components of body's immune defense. Macrophages have diverse roles in tissue homeostasis, development, and tissue repair following injury. Adult bone marrow monocytes can give rise to tissue-resident macrophages during infection or inflammatory reactions, besides self-replication of tissue resident macrophages. Lysophosphatidic acid (LPA), a lipid by-product of autotaxin activity, is involved in cancer, vascular defects, and neural tissue, but is largely unexplored in immune system. Here, we reveal an unexpected function of LPA that transfigures CD11b+murine monocytes into F4/80+macrophages. LPA-stimulated Akt/mTOR signaling is critical for LPA-mediated macrophage development in mice. Additionally, transcriptome analysis reveals that PPARγ is the key transcriptional regulator in the development of LPA-induced macrophages. In humans, LPA mediates macrophage formation following similar pathways. These findings identify a critical role for LPA in regulating innate immune system.
authors.affiliation: Department of Infectious Disease Biology, Institute of Life Sciences (An Autonomous Institute of Department of Biotechnology New Delhi), Bhubaneswar, India; and.|School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Rashmi
authors.identifier: 0000-0002-4794-3124
authors.initials: R
authors.lastname: Ray
authors.affiliation: Department of Infectious Disease Biology, Institute of Life Sciences (An Autonomous Institute of Department of Biotechnology New Delhi), Bhubaneswar, India; and.
authors.forename: Vivek
authors.identifier: 0000-0003-4539-8916
authors.initials: V
authors.lastname: Rai
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D015151:Immunoblotting; D008246:Lysophospholipids / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D047495:PPAR gamma / Q000276:immunology
chemical_list: D008246:Lysophospholipids; D047495:PPAR gamma; C032881:lysophosphatidic acid