THESIS
2019
xiii, 134 pages : illustrations (some color) ; 30 cm
Abstract
Resident immune cells in mucosal barriers of vertebrates, such as tissue-resident
macrophages (TRMs), are highly heterogeneous populations that play crucial roles in
maintenance of tissue homeostasis, which still lack comprehensive understanding. Here I report
the identification and characterization of three novel non-hematopoietic derived immune cells
in three major mucous barrier tissues-epidermis, gill and intestine of zebrafish. By using IR-LEGO
system, I firstly identify two morphological similar mpeg1
+ populations in these tissues,
one is widely distributed conventional TRMs generated from AGM, the other is locally
restricted mpeg1
+ cells with non-hematopoietic origin. RNA-sequencing analysis of these two
populations reveals that locally restricted mpeg1
+ populations in al...[
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Resident immune cells in mucosal barriers of vertebrates, such as tissue-resident
macrophages (TRMs), are highly heterogeneous populations that play crucial roles in
maintenance of tissue homeostasis, which still lack comprehensive understanding. Here I report
the identification and characterization of three novel non-hematopoietic derived immune cells
in three major mucous barrier tissues-epidermis, gill and intestine of zebrafish. By using IR-LEGO
system, I firstly identify two morphological similar mpeg1
+ populations in these tissues,
one is widely distributed conventional TRMs generated from AGM, the other is locally
restricted mpeg1
+ cells with non-hematopoietic origin. RNA-sequencing analysis of these two
populations reveals that locally restricted mpeg1
+ populations in all three tissues are myeloidlike
cells (MLCs) which share the highest similarities with TRMs in transcriptome levels.
Intriguingly, further fate mapping studies demonstrate that MLCs in epidermis are generated
from ectoderm while those in gill and intestine are derived from endoderm. Unlike TRMs,
MLCs in three tissues respond neither to tissue injury nor bacterial infection, but rather sample
soluble antigens from external environment, which are depend on tight-junction mediated
formation of transepithelial protrusions. After soluble antigen uptake, MLCs in epidermis
transfer those antigens to TRMs (Langerhans Cells) through apoptosis-phagocytosis axis, for
which we designate this MLCs as “metaphocyte”. This phenomenon suggests an
immunological role of metaphocytes. In line with this, MLCs in gill also participate in
regulating interferon productions upon poly(I:C) stimulation. My studies document the
existence of non-hematopoietic derived myeloid-like cells that manifest distinct function from
conventional TRMs in mucosal barriers and open a new paradigm for investigation the
heterogeneities of resident immune cells of vertabrates.
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