CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin

A. Flores-Langarica*, K. Müller Luda, E. K. Persson, C. N. Cook, S. Bobat, J. L. Marshall, M. W. Dahlgren, K. Hägerbrand, K. M. Toellner, M. D. Goodall, D. R. Withers, I. R. Henderson, B. Johansson Lindbom, A. F. Cunningham, W. W. Agace

*Corresponding author for this work

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Abstract

Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103CD11b+(DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+ CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4β 7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.

Original languageEnglish
JournalMucosal Immunology
Volume11
Issue number3
Pages (from-to)681-692
ISSN1933-0219
DOIs
Publication statusPublished - 1 May 2018

Cite this

Flores-Langarica, A., Müller Luda, K., Persson, E. K., Cook, C. N., Bobat, S., Marshall, J. L., ... Agace, W. W. (2018). CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin. Mucosal Immunology, 11(3), 681-692. https://doi.org/10.1038/mi.2017.105
Flores-Langarica, A. ; Müller Luda, K. ; Persson, E. K. ; Cook, C. N. ; Bobat, S. ; Marshall, J. L. ; Dahlgren, M. W. ; Hägerbrand, K. ; Toellner, K. M. ; Goodall, M. D. ; Withers, D. R. ; Henderson, I. R. ; Johansson Lindbom, B. ; Cunningham, A. F. ; Agace, W. W. / CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin. In: Mucosal Immunology. 2018 ; Vol. 11, No. 3. pp. 681-692.
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title = "CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin",
abstract = "Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+ CD11b+(DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+ CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4β 7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.",
author = "A. Flores-Langarica and {M{\"u}ller Luda}, K. and Persson, {E. K.} and Cook, {C. N.} and S. Bobat and Marshall, {J. L.} and Dahlgren, {M. W.} and K. H{\"a}gerbrand and Toellner, {K. M.} and Goodall, {M. D.} and Withers, {D. R.} and Henderson, {I. R.} and {Johansson Lindbom}, B. and Cunningham, {A. F.} and Agace, {W. W.}",
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Flores-Langarica, A, Müller Luda, K, Persson, EK, Cook, CN, Bobat, S, Marshall, JL, Dahlgren, MW, Hägerbrand, K, Toellner, KM, Goodall, MD, Withers, DR, Henderson, IR, Johansson Lindbom, B, Cunningham, AF & Agace, WW 2018, 'CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin', Mucosal Immunology, vol. 11, no. 3, pp. 681-692. https://doi.org/10.1038/mi.2017.105

CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin. / Flores-Langarica, A.; Müller Luda, K.; Persson, E. K.; Cook, C. N.; Bobat, S.; Marshall, J. L.; Dahlgren, M. W.; Hägerbrand, K.; Toellner, K. M.; Goodall, M. D.; Withers, D. R.; Henderson, I. R.; Johansson Lindbom, B.; Cunningham, A. F.; Agace, W. W.

In: Mucosal Immunology, Vol. 11, No. 3, 01.05.2018, p. 681-692.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin

AU - Flores-Langarica, A.

AU - Müller Luda, K.

AU - Persson, E. K.

AU - Cook, C. N.

AU - Bobat, S.

AU - Marshall, J. L.

AU - Dahlgren, M. W.

AU - Hägerbrand, K.

AU - Toellner, K. M.

AU - Goodall, M. D.

AU - Withers, D. R.

AU - Henderson, I. R.

AU - Johansson Lindbom, B.

AU - Cunningham, A. F.

AU - Agace, W. W.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+ CD11b+(DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+ CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4β 7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.

AB - Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+ CD11b+(DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+ CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4β 7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.

U2 - 10.1038/mi.2017.105

DO - 10.1038/mi.2017.105

M3 - Journal article

VL - 11

SP - 681

EP - 692

JO - Mucosal Immunology

JF - Mucosal Immunology

SN - 1933-0219

IS - 3

ER -

Flores-Langarica A, Müller Luda K, Persson EK, Cook CN, Bobat S, Marshall JL et al. CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin. Mucosal Immunology. 2018 May 1;11(3):681-692. https://doi.org/10.1038/mi.2017.105