Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

Dror S. Shouval; Amlan Biswas; Jeremy A. Goettel; Katelyn McCann; Evan Conaway; Naresh S. Redhu; Ivan D. Mascanfroni; Ziad AlAdham; Sydney Lavoie; Mouna Ibourk; Deanna D. Nguyen; Janneke N. Samsom; Johanna C. Escher; Raz Somech; Batia Weiss; Rita Beier; Laurie S. Conklin; Christen L. Ebens; Fernanda G M S Santos; Alexandre R. Ferreira; Mary Sherlock; Atul K. Bhan; Werner Müller; J. Rodrigo Mora; Francisco J. Quintana; Christoph Klein; Aleixo M. Muise; BruceH Horwitz; Scott B. Snapper

doi:10.1016/j.immuni.2014.03.011

Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

Dror S. Shouval, Amlan Biswas, Jeremy A. Goettel, Katelyn McCann, Evan Conaway, Naresh S. Redhu, Ivan D. Mascanfroni, Ziad AlAdham, Sydney Lavoie, Mouna Ibourk, Deanna D. Nguyen, Janneke N. Samsom, Johanna C. Escher, Raz Somech, Batia Weiss, Rita Beier, Laurie S. Conklin, Christen L. Ebens, Fernanda G M S Santos, Alexandre R. FerreiraMary Sherlock, Atul K. Bhan, Werner Müller, J. Rodrigo Mora, Francisco J. Quintana, Christoph Klein, Aleixo M. Muise, BruceH Horwitz, Scott B. Snapper

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

Abstract

Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4+ Tcell transfer, Rag2-/-Il10rb-/- mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb-/- anti-inflammatory macrophages ameliorated colitis induction by WT CD4+ Tcells in Rag2-/-Il10rb-/- mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans. © 2014 Elsevier Inc.

Original language	English
Pages (from-to)	706-719
Number of pages	13
Journal	Immunity
Volume	40
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2014.03.011
Publication status	Published - 15 May 2014

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Shouval, D. S., Biswas, A., Goettel, J. A., McCann, K., Conaway, E., Redhu, N. S., Mascanfroni, I. D., AlAdham, Z., Lavoie, S., Ibourk, M., Nguyen, D. D., Samsom, J. N., Escher, J. C., Somech, R., Weiss, B., Beier, R., Conklin, L. S., Ebens, C. L., Santos, F. G. M. S., ... Snapper, S. B. (2014). Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity, 40(5), 706-719. https://doi.org/10.1016/j.immuni.2014.03.011

@article{cd6251902b98435c9b464c8d8703e84b,

title = "Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function",

abstract = "Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4+ Tcell transfer, Rag2-/-Il10rb-/- mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb-/- anti-inflammatory macrophages ameliorated colitis induction by WT CD4+ Tcells in Rag2-/-Il10rb-/- mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans. {\textcopyright} 2014 Elsevier Inc.",

author = "Shouval, {Dror S.} and Amlan Biswas and Goettel, {Jeremy A.} and Katelyn McCann and Evan Conaway and Redhu, {Naresh S.} and Mascanfroni, {Ivan D.} and Ziad AlAdham and Sydney Lavoie and Mouna Ibourk and Nguyen, {Deanna D.} and Samsom, {Janneke N.} and Escher, {Johanna C.} and Raz Somech and Batia Weiss and Rita Beier and Conklin, {Laurie S.} and Ebens, {Christen L.} and Santos, {Fernanda G M S} and Ferreira, {Alexandre R.} and Mary Sherlock and Bhan, {Atul K.} and Werner M{\"u}ller and Mora, {J. Rodrigo} and Quintana, {Francisco J.} and Christoph Klein and Muise, {Aleixo M.} and BruceH Horwitz and Snapper, {Scott B.}",

year = "2014",

month = may,

day = "15",

doi = "10.1016/j.immuni.2014.03.011",

language = "English",

volume = "40",

pages = "706--719",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "5",

}

Shouval, DS, Biswas, A, Goettel, JA, McCann, K, Conaway, E, Redhu, NS, Mascanfroni, ID, AlAdham, Z, Lavoie, S, Ibourk, M, Nguyen, DD, Samsom, JN, Escher, JC, Somech, R, Weiss, B, Beier, R, Conklin, LS, Ebens, CL, Santos, FGMS, Ferreira, AR, Sherlock, M, Bhan, AK, Müller, W, Mora, JR, Quintana, FJ, Klein, C, Muise, AM, Horwitz, B & Snapper, SB 2014, 'Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function', Immunity, vol. 40, no. 5, pp. 706-719. https://doi.org/10.1016/j.immuni.2014.03.011

TY - JOUR

T1 - Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

AU - Shouval, Dror S.

AU - Biswas, Amlan

AU - Goettel, Jeremy A.

AU - McCann, Katelyn

AU - Conaway, Evan

AU - Redhu, Naresh S.

AU - Mascanfroni, Ivan D.

AU - AlAdham, Ziad

AU - Lavoie, Sydney

AU - Ibourk, Mouna

AU - Nguyen, Deanna D.

AU - Samsom, Janneke N.

AU - Escher, Johanna C.

AU - Somech, Raz

AU - Weiss, Batia

AU - Beier, Rita

AU - Conklin, Laurie S.

AU - Ebens, Christen L.

AU - Santos, Fernanda G M S

AU - Ferreira, Alexandre R.

AU - Sherlock, Mary

AU - Bhan, Atul K.

AU - Müller, Werner

AU - Mora, J. Rodrigo

AU - Quintana, Francisco J.

AU - Klein, Christoph

AU - Muise, Aleixo M.

AU - Horwitz, BruceH

AU - Snapper, Scott B.

PY - 2014/5/15

Y1 - 2014/5/15

N2 - Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4+ Tcell transfer, Rag2-/-Il10rb-/- mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb-/- anti-inflammatory macrophages ameliorated colitis induction by WT CD4+ Tcells in Rag2-/-Il10rb-/- mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans. © 2014 Elsevier Inc.

AB - Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4+ Tcell transfer, Rag2-/-Il10rb-/- mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb-/- anti-inflammatory macrophages ameliorated colitis induction by WT CD4+ Tcells in Rag2-/-Il10rb-/- mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans. © 2014 Elsevier Inc.

U2 - 10.1016/j.immuni.2014.03.011

DO - 10.1016/j.immuni.2014.03.011

M3 - Article

C2 - 24792912

SN - 1074-7613

VL - 40

SP - 706

EP - 719

JO - Immunity

JF - Immunity

IS - 5

ER -

Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

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