RRC ID 47791
著者 Nonaka S, Ando Y, Kanetani T, Hoshi C, Nakai Y, Nainu F, Nagaosa K, Shiratsuchi A, Nakanishi Y.
タイトル Signaling pathway for phagocyte priming upon encounter with apoptotic cells.
ジャーナル J Biol Chem
Abstract The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity.
巻・号 292(19)
ページ 8059-8072
公開日 2017-5-12
DOI 10.1074/jbc.M116.769745
PII S0021-9258(20)41899-X
PMID 28325838
PMC PMC5427281
MeSH Animals Apoptosis* Cell Line Cell Nucleus / metabolism Cycloheximide / chemistry Cytoskeletal Proteins / metabolism DNA / analysis Drosophila Proteins / metabolism Drosophila melanogaster / metabolism Hemocytes / cytology Immunity, Innate Integrin alpha Chains / metabolism Membrane Proteins / metabolism Oncogene Protein v-crk / metabolism Phagocytes / cytology* Phagocytosis RNA Interference Repressor Proteins / metabolism Signal Transduction*
IF 4.238
引用数 13
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ショウジョウバエ 1762R-1