Frontline Science: Induction of experimental autoimmune encephalomyelitis mobilizes Th17-promoting myeloid derived suppressor cells to the lung

Justin D. Glenn, Charles Liu, Katharine Whartenby

Research output: Contribution to journalArticle

Abstract

Myeloid-derived suppressor cells (MDSCs) are a diverse group of cells that are recognized for their remarkable suppressive effects on pro-inflammatory T cells. The pleiotropic nature of these cells, however, has been demonstrated by their differential effects on immune responses in different settings. Our and others’ work has demonstrated suppressive effects of these cells. We previously demonstrated that these cells were mobilized to the lungs during experimental autoimmune encephalomyelitis (EAE), which is a murine model of multiple sclerosis, and potently inhibited CD8 + T cell responses against influenza infection. Interestingly, they appeared to have a lesser effect on CD4 + T cells, and in fact, others have demonstrated that spleen-derived MDSCs could actually promote Th17 differentiation. We sought to determine the role of lung-derived MDSCs on EAE pathogenesis, as excursion through the lungs by pathologic CNS-Ag targeted T cells was shown to be critical for EAE induction. Our results indicate a robust accumulation of granulocytic MDSCs in the lungs of mice during EAE, which could promote Th17 polarization, and which coincided with the trafficking of autoimmune-targeted T cells through the lungs. These studies underscore the pleiotropic effect of MDSCs on T cells and their potential pro-inflammatory phenotypes in neuro-inflammatory disease. Understanding both the intrinsic multifunctional nature of these cells and the ability to influence organ-specific targets such as the CNS from remote organs such as lungs will help to elucidate both mechanisms of disease and possible new therapeutic approaches.

Original languageEnglish (US)
JournalJournal of Leukocyte Biology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Lung
Human Influenza
Multiple Sclerosis
Myeloid-Derived Suppressor Cells
Spleen
Phenotype
Infection

Keywords

  • Experimental autoimmune encephalomyelitis
  • lung
  • monocytes
  • multiple sclerosis
  • myeloid derived suppressor cells
  • Th17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

@article{2301c68f7e744df5a3c48471df6ad705,
title = "Frontline Science: Induction of experimental autoimmune encephalomyelitis mobilizes Th17-promoting myeloid derived suppressor cells to the lung",
abstract = "Myeloid-derived suppressor cells (MDSCs) are a diverse group of cells that are recognized for their remarkable suppressive effects on pro-inflammatory T cells. The pleiotropic nature of these cells, however, has been demonstrated by their differential effects on immune responses in different settings. Our and others’ work has demonstrated suppressive effects of these cells. We previously demonstrated that these cells were mobilized to the lungs during experimental autoimmune encephalomyelitis (EAE), which is a murine model of multiple sclerosis, and potently inhibited CD8 + T cell responses against influenza infection. Interestingly, they appeared to have a lesser effect on CD4 + T cells, and in fact, others have demonstrated that spleen-derived MDSCs could actually promote Th17 differentiation. We sought to determine the role of lung-derived MDSCs on EAE pathogenesis, as excursion through the lungs by pathologic CNS-Ag targeted T cells was shown to be critical for EAE induction. Our results indicate a robust accumulation of granulocytic MDSCs in the lungs of mice during EAE, which could promote Th17 polarization, and which coincided with the trafficking of autoimmune-targeted T cells through the lungs. These studies underscore the pleiotropic effect of MDSCs on T cells and their potential pro-inflammatory phenotypes in neuro-inflammatory disease. Understanding both the intrinsic multifunctional nature of these cells and the ability to influence organ-specific targets such as the CNS from remote organs such as lungs will help to elucidate both mechanisms of disease and possible new therapeutic approaches.",
keywords = "Experimental autoimmune encephalomyelitis, lung, monocytes, multiple sclerosis, myeloid derived suppressor cells, Th17",
author = "Glenn, {Justin D.} and Charles Liu and Katharine Whartenby",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/JLB.4HI0818-335R",
language = "English (US)",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",

}

TY - JOUR

T1 - Frontline Science

T2 - Induction of experimental autoimmune encephalomyelitis mobilizes Th17-promoting myeloid derived suppressor cells to the lung

AU - Glenn, Justin D.

AU - Liu, Charles

AU - Whartenby, Katharine

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Myeloid-derived suppressor cells (MDSCs) are a diverse group of cells that are recognized for their remarkable suppressive effects on pro-inflammatory T cells. The pleiotropic nature of these cells, however, has been demonstrated by their differential effects on immune responses in different settings. Our and others’ work has demonstrated suppressive effects of these cells. We previously demonstrated that these cells were mobilized to the lungs during experimental autoimmune encephalomyelitis (EAE), which is a murine model of multiple sclerosis, and potently inhibited CD8 + T cell responses against influenza infection. Interestingly, they appeared to have a lesser effect on CD4 + T cells, and in fact, others have demonstrated that spleen-derived MDSCs could actually promote Th17 differentiation. We sought to determine the role of lung-derived MDSCs on EAE pathogenesis, as excursion through the lungs by pathologic CNS-Ag targeted T cells was shown to be critical for EAE induction. Our results indicate a robust accumulation of granulocytic MDSCs in the lungs of mice during EAE, which could promote Th17 polarization, and which coincided with the trafficking of autoimmune-targeted T cells through the lungs. These studies underscore the pleiotropic effect of MDSCs on T cells and their potential pro-inflammatory phenotypes in neuro-inflammatory disease. Understanding both the intrinsic multifunctional nature of these cells and the ability to influence organ-specific targets such as the CNS from remote organs such as lungs will help to elucidate both mechanisms of disease and possible new therapeutic approaches.

AB - Myeloid-derived suppressor cells (MDSCs) are a diverse group of cells that are recognized for their remarkable suppressive effects on pro-inflammatory T cells. The pleiotropic nature of these cells, however, has been demonstrated by their differential effects on immune responses in different settings. Our and others’ work has demonstrated suppressive effects of these cells. We previously demonstrated that these cells were mobilized to the lungs during experimental autoimmune encephalomyelitis (EAE), which is a murine model of multiple sclerosis, and potently inhibited CD8 + T cell responses against influenza infection. Interestingly, they appeared to have a lesser effect on CD4 + T cells, and in fact, others have demonstrated that spleen-derived MDSCs could actually promote Th17 differentiation. We sought to determine the role of lung-derived MDSCs on EAE pathogenesis, as excursion through the lungs by pathologic CNS-Ag targeted T cells was shown to be critical for EAE induction. Our results indicate a robust accumulation of granulocytic MDSCs in the lungs of mice during EAE, which could promote Th17 polarization, and which coincided with the trafficking of autoimmune-targeted T cells through the lungs. These studies underscore the pleiotropic effect of MDSCs on T cells and their potential pro-inflammatory phenotypes in neuro-inflammatory disease. Understanding both the intrinsic multifunctional nature of these cells and the ability to influence organ-specific targets such as the CNS from remote organs such as lungs will help to elucidate both mechanisms of disease and possible new therapeutic approaches.

KW - Experimental autoimmune encephalomyelitis

KW - lung

KW - monocytes

KW - multiple sclerosis

KW - myeloid derived suppressor cells

KW - Th17

UR - http://www.scopus.com/inward/record.url?scp=85061586155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061586155&partnerID=8YFLogxK

U2 - 10.1002/JLB.4HI0818-335R

DO - 10.1002/JLB.4HI0818-335R

M3 - Article

C2 - 30762897

AN - SCOPUS:85061586155

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

ER -