Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation

 Han et al. Nature 539: 570-574, 2016

Speaker: Shang-Yi Lin (林尚儀)                                  Time: 13:00~14:00, May 24, 2017

Commentator: Dr. Chi-Chang Shieh (謝奇璋老師)     Place: Room 601

Abstract:

Both professional and non-professional phagocytes are involved in the removal of apoptotic cells and particles¹. However, whether they communicate with each other during cell clearance, and how this impacts inflammation, is still unknown². In this study, the authors showed that macrophages (professional phagocytes) released insulin-like growth factor 1 (IGF-1) when exposed to apoptotic cell and/or inflammation-associated cytokines. IGF-1 is associated with tissue repair, inflammation dampening, and tissue morphogenesis³. In non-specialized phagocytic cell line LR73B, binding of IGF-1 to its receptor (IGF-1R) reduced uptake of apoptotic cells, but enhanced uptake of microvesicles. Of note, such effect was not observed in macrophages. Furthermore, in an airway inflammation model, cytokines, such as IL-4, produced by resident basophils and/or type-2 innate lymphoid cells (ILC2s) could elicit production of IGF-1 and secretion of anti-inflammatory microvesicles from alveolar macrophages. IGF-1 enhanced engulfment of these microvesicles and reduced inflammatory cytokine production by airway epithelial cells (non-professional phagocytes). In addition, mice lacking IGF-1R in airway epithelial cells had greater airway inflammation than the wild-type mice following sensitization and challenge with house dust mite. Collectively, these results indicate that secretion of IGF-1 and microvesicles by macrophages redirects phagocytosis by non-professional phagocytes and reduces inflammatory response. Thus, modulation of the IGF-1－IGF-1R signaling axis may be a promising therapeutic strategy for airway hyper-responsiveness to allergens.

References:

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2.     Green, D. R. The end and after: how dying cells impact the living organism. Immunity 35, 441–444 (2011).

3.     Werner, S. & Grose, R. Regulation of wound healing by growth factors and cytokines. Physiol. Rev. 83, 835–870 (2003).