IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses

Andreas Schlitzer; Naomi McGovern; Pearline Teo; Teresa Zelante; Koji Atarashi; Donovan Low; Adrian W S Ho; Peter See; Amanda Shin; Pavandip Singh Wasan; Guillaume Hoeffel; Benoit Malleret; Alexander Heiseke; Samantha Chew; Laura Jardine; Harriet A Purvis; Catharien M U Hilkens; John Tam; Michael Poidinger; E Richard Stanley; Anne B Krug; Laurent Renia; Baalasubramanian Sivasankar; Lai Guan Ng; Matthew Collin; Paola Ricciardi-Castagnoli; Kenya Honda; Muzlifah Haniffa; Florent Ginhoux

doi:10.1016/j.immuni.2013.04.011

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses

Andreas Schlitzer, Naomi McGovern, Pearline Teo, Teresa Zelante, Koji Atarashi, Donovan Low, Adrian W S Ho, Peter See, Amanda Shin, Pavandip Singh Wasan, Guillaume Hoeffel, Benoit Malleret, Alexander Heiseke, Samantha Chew, Laura Jardine, Harriet A Purvis, Catharien M U Hilkens, John Tam, Michael Poidinger, E Richard StanleyAnne B Krug, Laurent Renia, Baalasubramanian Sivasankar, Lai Guan Ng, Matthew Collin, Paola Ricciardi-Castagnoli, Kenya Honda, Muzlifah Haniffa, Florent Ginhoux

Inflammation Biology

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

658 Citations (Scopus)

Abstract

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.

Original language	English
Pages (from-to)	970-983
Number of pages	14
Journal	Immunity
Volume	38
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2013.04.011
Publication status	Published - 23 May 2013

Keywords

Animals
Antigens, CD11b
Antigens, CD24
Aspergillus fumigatus
Cell Differentiation
Dendritic Cells
Humans
Interferon Regulatory Factors
Interleukin-17
Interleukin-23
Intestinal Mucosa
Macrophages
Mice
Receptors, IgG
Respiratory Mucosa
Th17 Cells
fms-Like Tyrosine Kinase 3

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Schlitzer, A., McGovern, N., Teo, P., Zelante, T., Atarashi, K., Low, D., Ho, A. W. S., See, P., Shin, A., Wasan, P. S., Hoeffel, G., Malleret, B., Heiseke, A., Chew, S., Jardine, L., Purvis, H. A., Hilkens, C. M. U., Tam, J., Poidinger, M., ... Ginhoux, F. (2013). IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity, 38(5), 970-983. https://doi.org/10.1016/j.immuni.2013.04.011

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title = "IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses",

abstract = "Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.",

keywords = "Animals, Antigens, CD11b, Antigens, CD24, Aspergillus fumigatus, Cell Differentiation, Dendritic Cells, Humans, Interferon Regulatory Factors, Interleukin-17, Interleukin-23, Intestinal Mucosa, Macrophages, Mice, Receptors, IgG, Respiratory Mucosa, Th17 Cells, fms-Like Tyrosine Kinase 3",

author = "Andreas Schlitzer and Naomi McGovern and Pearline Teo and Teresa Zelante and Koji Atarashi and Donovan Low and Ho, {Adrian W S} and Peter See and Amanda Shin and Wasan, {Pavandip Singh} and Guillaume Hoeffel and Benoit Malleret and Alexander Heiseke and Samantha Chew and Laura Jardine and Purvis, {Harriet A} and Hilkens, {Catharien M U} and John Tam and Michael Poidinger and Stanley, {E Richard} and Krug, {Anne B} and Laurent Renia and Baalasubramanian Sivasankar and Ng, {Lai Guan} and Matthew Collin and Paola Ricciardi-Castagnoli and Kenya Honda and Muzlifah Haniffa and Florent Ginhoux",

year = "2013",

month = may,

day = "23",

doi = "10.1016/j.immuni.2013.04.011",

language = "English",

volume = "38",

pages = "970--983",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

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Schlitzer, A, McGovern, N, Teo, P, Zelante, T, Atarashi, K, Low, D, Ho, AWS, See, P, Shin, A, Wasan, PS, Hoeffel, G, Malleret, B, Heiseke, A, Chew, S, Jardine, L, Purvis, HA, Hilkens, CMU, Tam, J, Poidinger, M, Stanley, ER, Krug, AB, Renia, L, Sivasankar, B, Ng, LG, Collin, M, Ricciardi-Castagnoli, P, Honda, K, Haniffa, M & Ginhoux, F 2013, 'IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses', Immunity, vol. 38, no. 5, pp. 970-983. https://doi.org/10.1016/j.immuni.2013.04.011

TY - JOUR

T1 - IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses

AU - Schlitzer, Andreas

AU - McGovern, Naomi

AU - Teo, Pearline

AU - Zelante, Teresa

AU - Atarashi, Koji

AU - Low, Donovan

AU - Ho, Adrian W S

AU - See, Peter

AU - Shin, Amanda

AU - Wasan, Pavandip Singh

AU - Hoeffel, Guillaume

AU - Malleret, Benoit

AU - Heiseke, Alexander

AU - Chew, Samantha

AU - Jardine, Laura

AU - Purvis, Harriet A

AU - Hilkens, Catharien M U

AU - Tam, John

AU - Poidinger, Michael

AU - Stanley, E Richard

AU - Krug, Anne B

AU - Renia, Laurent

AU - Sivasankar, Baalasubramanian

AU - Ng, Lai Guan

AU - Collin, Matthew

AU - Ricciardi-Castagnoli, Paola

AU - Honda, Kenya

AU - Haniffa, Muzlifah

AU - Ginhoux, Florent

PY - 2013/5/23

Y1 - 2013/5/23

N2 - Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.

AB - Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.

KW - Animals

KW - Antigens, CD11b

KW - Antigens, CD24

KW - Aspergillus fumigatus

KW - Cell Differentiation

KW - Dendritic Cells

KW - Humans

KW - Interferon Regulatory Factors

KW - Interleukin-17

KW - Interleukin-23

KW - Intestinal Mucosa

KW - Macrophages

KW - Mice

KW - Receptors, IgG

KW - Respiratory Mucosa

KW - Th17 Cells

KW - fms-Like Tyrosine Kinase 3

U2 - 10.1016/j.immuni.2013.04.011

DO - 10.1016/j.immuni.2013.04.011

M3 - Article

C2 - 23706669

SN - 1074-7613

VL - 38

SP - 970

EP - 983

JO - Immunity

JF - Immunity

IS - 5

ER -

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses

Abstract

Keywords

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