Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 174

Thymic dendritic cells include 2 conventional dendritic cell subtypes: CD8 low ,
Sirp and CD8 high ,Sirp , which have different origins. CD8 low ,Sirp thymic

dendritic cells have a greater capacity to activate T-regulatory cells, at least in vitro.

α+ α − α+

3.15 Myeloid-Derived Suppressor Cells

Myeloid-derived suppressor cells constitute a special compartment of the immune
system of myeloid origin that includes myeloid progenitor cells and immature
myeloid cells (immature macrophages, granulocytes, and dendritic cells). In healthy
subjects, immature myeloid cells generated in the bone marrow differentiate
into mature granulocytes, macrophages, or dendritic cells. On the other hand, in
pathological conditions, a partial immature myeloid cell pool differentiates into
mature myeloid-derived suppressor cells.
Myeloid-derived suppressor cells suppress T-cell responses, once they build
intercellular contact. In addition to suppression of adaptive immunity, myeloid
suppressors regulate innate immunity, as they modulate the cytokine production of
macrophages. In addition, these cells promote tumor angiogenesis and metastasis.
Suppressive myeloid cells mature from immature myeloid cell population (that
arises from common myeloid progenitor cells) during inflammation, infection,
trauma, and some autoimmune diseases, as well as cancer. 190 In normal conditions,
immature myeloid cells do not give rise to suppressor cells. They reside in the bone
marrow, but not in secondary lymphoid organs. In normal conditions, immature
myeloid cells differentiate into dendritic cells, granulocytes, or macrophages.
This differentiation is promoted by numerous factors (stem cell factor, colony-
stimulating factors [CSF1-CSF3], vascular endothelial growth factor, interleukins
IL3 and IL6, stem cell protein Tyr kinase receptor STK1 [or fetal liver kinase FLK2],
Notch, and prostaglandins).
In pathological conditions, this usual differentiation of immature myeloid cells
that accumulate in abnormal tissues is prevented. Instead, resident immature
myeloid cells are transformed into activated myeloid-derived suppressor cells. In
addition to usual expansion agents (CSF1-CSF3, SCF, VEGF, etc.) this abnormal
transformation is caused by many factors, such as interferon-

γ

, Toll-like receptor
ligands, interleukins IL4, IL10, IL12 and IL13, transforming growth factor-

β

,
calcium-binding proteins S100A8 and S100A9, complement component-5A, CC-
and CXC-chemokine ligands CCL2, CXCL5, and CXCL12, cyclooxygenase-2, and
matrix metallopeptidase MMP9 [ 316 ]. Most of these factors trigger the JaK2-
STAT3 axis.

190 In tumors, myeloid-derived suppressor cells can be distinguished from tumor-associated mac-
rophages by their granulocytic morphology, lower expression of F4/80, and elevated expression of
both arginase-1 and NOS2.