TY - JOUR
T1 - Functional macrophage heterogeneity in a mouse model of autoimmune central nervous system pathology
AU - London, Anat
AU - Benhar, Inbal
AU - Mattapallil, Mary J.
AU - Mack, Matthias
AU - Caspi, Rachel R.
AU - Schwartz, Michal
PY - 2013/4/1
Y1 - 2013/4/1
N2 - Functional macrophage heterogeneity is well appreciated outside the CNS in wound healing and cancer, and was recently also demonstrated in several CNS compartments after "sterile" insults. Yet, such heterogeneity was largely overlooked in the context of inflammatory autoimmune pathology, in which macrophages were mainly associated with disease induction and propagation. In this article, we show the diversity of monocyte-derived macrophages along the course of experimental autoimmune uveitis, an inflammatory condition affecting the ocular system, serving as a model for CNS autoimmune pathology. Disease induction resulted in the appearance of a distinct myeloid population in the retina, and in the infiltration of monocyte-derived macrophages that were absent from control eyes. During the disease course, the frequency of CX 3CR1high infiltrating macrophages that express markers associated with inflammation-resolving activity was increased, along with a decrease in the frequency of inflammation-associated Ly6C+ macrophages. Inhibition of monocyte infiltration at the induction phase of experimental autoimmune uveitis prevented disease onset, whereas monocyte depletion at the resolution phase resulted in a decrease in Foxp3+ regulatory T cells and in exacerbated disease. Thus, monocyte-derived macrophages display distinct phenotypes throughout the disease course, even in an immune-induced pathology, reflecting their differential roles in disease induction and resolution.
AB - Functional macrophage heterogeneity is well appreciated outside the CNS in wound healing and cancer, and was recently also demonstrated in several CNS compartments after "sterile" insults. Yet, such heterogeneity was largely overlooked in the context of inflammatory autoimmune pathology, in which macrophages were mainly associated with disease induction and propagation. In this article, we show the diversity of monocyte-derived macrophages along the course of experimental autoimmune uveitis, an inflammatory condition affecting the ocular system, serving as a model for CNS autoimmune pathology. Disease induction resulted in the appearance of a distinct myeloid population in the retina, and in the infiltration of monocyte-derived macrophages that were absent from control eyes. During the disease course, the frequency of CX 3CR1high infiltrating macrophages that express markers associated with inflammation-resolving activity was increased, along with a decrease in the frequency of inflammation-associated Ly6C+ macrophages. Inhibition of monocyte infiltration at the induction phase of experimental autoimmune uveitis prevented disease onset, whereas monocyte depletion at the resolution phase resulted in a decrease in Foxp3+ regulatory T cells and in exacerbated disease. Thus, monocyte-derived macrophages display distinct phenotypes throughout the disease course, even in an immune-induced pathology, reflecting their differential roles in disease induction and resolution.
UR - http://www.scopus.com/inward/record.url?scp=84875412113&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1202076
DO - 10.4049/jimmunol.1202076
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C2 - 23447691
AN - SCOPUS:84875412113
SN - 0022-1767
VL - 190
SP - 3570
EP - 3578
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -