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Lysophosphatidic acid converts monocytes into macrophages in both mice and humans

Rashmi Ray and Vivek Rai

Key points

  • LPA converts monocytes into macrophages.

  • LPA mediates macrophage formation via Akt/mTor pathway and PPARγ is master regulator of LPA derived macrophages.

Abstract

Monocytes and macrophages represent critical arms of the innate immune system and are considered regulators and effectors of inflammation and 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 an important component of body's immune defense. Macrophages have diverse roles in tissue homeostasis, development as well as 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 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/m-TOR 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 critical role for LPA in regulating innate immune system.

  • Submitted October 3, 2016.
  • Accepted December 23, 2016.