Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation

Anthony Huggins; Nikolaos Paschalidis; Roderick J Flower; Mauro Perretti; Fulvio D'Acquisto

doi:10.1096/fj.08-119040

Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation

Anthony Huggins, Nikolaos Paschalidis, Roderick J Flower, Mauro Perretti, Fulvio D'Acquisto

Research output: Contribution to journal › Article › peer-review

Abstract

Dendritic cells play a key role in the adaptive immune system by influencing T-cell differentiation. Annexin-1 (Anx-A1) has recently been shown to modulate the adaptive immune response by regulating T-cell activation and differentiation. Here we investigated the role of endogenous Anx-A1 in dendritic cells as major cellular counterpart of T-cell-driven immune response. We found that Anx-A1(-/-) bone marrow-derived dendritic cells show an increased number of CD11c(+) cells expressing high levels of some maturation markers, such as CD40, CD54, and CD80, coupled to a decreased capacity to take up antigen compared to control Anx-A1(+/+) cells. However, analysis of LPS-treated dendritic cells from Anx-A1(-/-) mice demonstrated a diminished up-regulation of maturation markers, a decreased migratory activity in vivo, and an attenuated production of the inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-12. This defect was also accompanied by impaired nuclear factor (NF)-kappaB/DNA-binding activity and lack of Anx-A1 signaling, as demonstrated by the reduced activation of extracellular-signal regulated kinase (ERK)1/2 and Akt compared to cells from control littermates. As a consequence of this phenotype, Anx-A1(-/-) dendritic cells showed an impaired capacity to stimulate T-cell proliferation and differentiation in mixed leukocyte reaction. Together, these findings suggest that inhibition of Anx-A1 expression or function in dendritic cells might represent a useful way to modulate the adaptive immune response and pathogen-induced T-cell-driven immune diseases.

Original language	English
Pages (from-to)	985-96
Number of pages	12
Journal	FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume	23
Issue number	4
DOIs	https://doi.org/10.1096/fj.08-119040
Publication status	Published - Apr 2009

Keywords

Animals
Annexin A1
Antigen-Presenting Cells
B7-1 Antigen
Biomarkers
Bone Marrow Cells
CD11c Antigen
CD40 Antigens
Cell Differentiation
Cell Movement
Cells, Cultured
Cytokines
Dendritic Cells
Dextrans
Fluorescein-5-isothiocyanate
Fluorescent Dyes
Lipopolysaccharides
Lymphocyte Culture Test, Mixed
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
T-Lymphocytes
Time Factors
Up-Regulation
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1096/fj.08-119040

Cite this

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title = "Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation",

abstract = "Dendritic cells play a key role in the adaptive immune system by influencing T-cell differentiation. Annexin-1 (Anx-A1) has recently been shown to modulate the adaptive immune response by regulating T-cell activation and differentiation. Here we investigated the role of endogenous Anx-A1 in dendritic cells as major cellular counterpart of T-cell-driven immune response. We found that Anx-A1(-/-) bone marrow-derived dendritic cells show an increased number of CD11c(+) cells expressing high levels of some maturation markers, such as CD40, CD54, and CD80, coupled to a decreased capacity to take up antigen compared to control Anx-A1(+/+) cells. However, analysis of LPS-treated dendritic cells from Anx-A1(-/-) mice demonstrated a diminished up-regulation of maturation markers, a decreased migratory activity in vivo, and an attenuated production of the inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-12. This defect was also accompanied by impaired nuclear factor (NF)-kappaB/DNA-binding activity and lack of Anx-A1 signaling, as demonstrated by the reduced activation of extracellular-signal regulated kinase (ERK)1/2 and Akt compared to cells from control littermates. As a consequence of this phenotype, Anx-A1(-/-) dendritic cells showed an impaired capacity to stimulate T-cell proliferation and differentiation in mixed leukocyte reaction. Together, these findings suggest that inhibition of Anx-A1 expression or function in dendritic cells might represent a useful way to modulate the adaptive immune response and pathogen-induced T-cell-driven immune diseases.",

keywords = "Animals, Annexin A1, Antigen-Presenting Cells, B7-1 Antigen, Biomarkers, Bone Marrow Cells, CD11c Antigen, CD40 Antigens, Cell Differentiation, Cell Movement, Cells, Cultured, Cytokines, Dendritic Cells, Dextrans, Fluorescein-5-isothiocyanate, Fluorescent Dyes, Lipopolysaccharides, Lymphocyte Culture Test, Mixed, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, T-Lymphocytes, Time Factors, Up-Regulation, Journal Article, Research Support, Non-U.S. Gov't",

author = "Anthony Huggins and Nikolaos Paschalidis and Flower, {Roderick J} and Mauro Perretti and Fulvio D'Acquisto",

year = "2009",

month = apr,

doi = "10.1096/fj.08-119040",

language = "English",

volume = "23",

pages = "985--96",

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issn = "0892-6638",

publisher = "FASEB",

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TY - JOUR

T1 - Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation

AU - Huggins, Anthony

AU - Paschalidis, Nikolaos

AU - Flower, Roderick J

AU - Perretti, Mauro

AU - D'Acquisto, Fulvio

PY - 2009/4

Y1 - 2009/4

N2 - Dendritic cells play a key role in the adaptive immune system by influencing T-cell differentiation. Annexin-1 (Anx-A1) has recently been shown to modulate the adaptive immune response by regulating T-cell activation and differentiation. Here we investigated the role of endogenous Anx-A1 in dendritic cells as major cellular counterpart of T-cell-driven immune response. We found that Anx-A1(-/-) bone marrow-derived dendritic cells show an increased number of CD11c(+) cells expressing high levels of some maturation markers, such as CD40, CD54, and CD80, coupled to a decreased capacity to take up antigen compared to control Anx-A1(+/+) cells. However, analysis of LPS-treated dendritic cells from Anx-A1(-/-) mice demonstrated a diminished up-regulation of maturation markers, a decreased migratory activity in vivo, and an attenuated production of the inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-12. This defect was also accompanied by impaired nuclear factor (NF)-kappaB/DNA-binding activity and lack of Anx-A1 signaling, as demonstrated by the reduced activation of extracellular-signal regulated kinase (ERK)1/2 and Akt compared to cells from control littermates. As a consequence of this phenotype, Anx-A1(-/-) dendritic cells showed an impaired capacity to stimulate T-cell proliferation and differentiation in mixed leukocyte reaction. Together, these findings suggest that inhibition of Anx-A1 expression or function in dendritic cells might represent a useful way to modulate the adaptive immune response and pathogen-induced T-cell-driven immune diseases.

AB - Dendritic cells play a key role in the adaptive immune system by influencing T-cell differentiation. Annexin-1 (Anx-A1) has recently been shown to modulate the adaptive immune response by regulating T-cell activation and differentiation. Here we investigated the role of endogenous Anx-A1 in dendritic cells as major cellular counterpart of T-cell-driven immune response. We found that Anx-A1(-/-) bone marrow-derived dendritic cells show an increased number of CD11c(+) cells expressing high levels of some maturation markers, such as CD40, CD54, and CD80, coupled to a decreased capacity to take up antigen compared to control Anx-A1(+/+) cells. However, analysis of LPS-treated dendritic cells from Anx-A1(-/-) mice demonstrated a diminished up-regulation of maturation markers, a decreased migratory activity in vivo, and an attenuated production of the inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-12. This defect was also accompanied by impaired nuclear factor (NF)-kappaB/DNA-binding activity and lack of Anx-A1 signaling, as demonstrated by the reduced activation of extracellular-signal regulated kinase (ERK)1/2 and Akt compared to cells from control littermates. As a consequence of this phenotype, Anx-A1(-/-) dendritic cells showed an impaired capacity to stimulate T-cell proliferation and differentiation in mixed leukocyte reaction. Together, these findings suggest that inhibition of Anx-A1 expression or function in dendritic cells might represent a useful way to modulate the adaptive immune response and pathogen-induced T-cell-driven immune diseases.

KW - Animals

KW - Annexin A1

KW - Antigen-Presenting Cells

KW - B7-1 Antigen

KW - Biomarkers

KW - Bone Marrow Cells

KW - CD11c Antigen

KW - CD40 Antigens

KW - Cell Differentiation

KW - Cell Movement

KW - Cells, Cultured

KW - Cytokines

KW - Dendritic Cells

KW - Dextrans

KW - Fluorescein-5-isothiocyanate

KW - Fluorescent Dyes

KW - Lipopolysaccharides

KW - Lymphocyte Culture Test, Mixed

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - T-Lymphocytes

KW - Time Factors

KW - Up-Regulation

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1096/fj.08-119040

DO - 10.1096/fj.08-119040

M3 - Article

C2 - 19029200

SN - 0892-6638

VL - 23

SP - 985

EP - 996

JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology

JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology

IS - 4

ER -