J Immunol 2019 02 9;202(4):1186-1199. Epub 2019 Jan 9.
The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
The phosphatidylserine receptor TIM4, encoded by , mediates the phagocytic uptake of apoptotic cells. We applied anti-chicken TIM4 mAbs in combination with reporter transgenes to dissect the function of TIM4 in the chick (). During development in ovo, TIM4 was present on the large majority of macrophages, but expression became more heterogeneous posthatch. Blood monocytes expressed KUL01, class II MHC, and mApple uniformly. Around 50% of monocytes were positive for surface TIM4. They also expressed many other monocyte-specific transcripts at a higher level than TIM4 monocytes. In liver, highly phagocytic TIM4 cells shared many transcripts with mammalian Kupffer cells and were associated with uptake of apoptotic cells. Although they expressed mRNA, Kupffer cells did not express the -mApple transgene, suggesting that additional transcriptional regulatory elements are required by these cells. By contrast, -mApple was detected in liver TIM4 and TIM4 cells, which were not phagocytic and were more abundant than Kupffer cells. These cells expressed alongside high levels of , , , and other markers associated with conventional dendritic cells in mice. In bursa, TIM4 was present on the cell surface of two populations. Like Kupffer cells, bursal TIM4 phagocytes coexpressed many receptors involved in apoptotic cell recognition. TIM4 cells appear to be a subpopulation of bursal B cells. In overview, TIM4 is associated with phagocytes that eliminate apoptotic cells in the chick. In the liver, TIM4 and reporters distinguished Kupffer cells from an abundant population of dendritic cell-like cells.