IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis

Matthew R. Macey; Jamie L. Sturgill; Johanna K. Morales; Yves T. Falanga; Joshua Morales; Sarah K. Norton; Nitin Yerram; Hoon Shim; Josephine Fernando; Alasdair M. Gifillan; Gregorio Gomez; Lawrence Schwartz; Carole Oskeritzian; Sarah Spiegel; Daniel Conrad; John J. Ryan

doi:10.4049/jimmunol.0903477

IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis

Matthew R. Macey, Jamie L. Sturgill, Johanna K. Morales, Yves T. Falanga, Joshua Morales, Sarah K. Norton, Nitin Yerram, Hoon Shim, Josephine Fernando, Alasdair M. Gifillan, Gregorio Gomez, Lawrence Schwartz, Carole Oskeritzian, Sarah Spiegel, Daniel Conrad, John J. Ryan

School of Medicine

Hackensack Meridian School of Medicine

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

Abstract

Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.

Original language	English
Pages (from-to)	4688-4695
Number of pages	8
Journal	Journal of Immunology
Volume	184
Issue number	9
DOIs	https://doi.org/10.4049/jimmunol.0903477
State	Published - May 1 2010

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.4049/jimmunol.0903477

Cite this

Macey, M. R., Sturgill, J. L., Morales, J. K., Falanga, Y. T., Morales, J., Norton, S. K., Yerram, N., Shim, H., Fernando, J., Gifillan, A. M., Gomez, G., Schwartz, L., Oskeritzian, C., Spiegel, S., Conrad, D., & Ryan, J. J. (2010). IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis. Journal of Immunology, 184(9), 4688-4695. https://doi.org/10.4049/jimmunol.0903477

@article{9698c547d2ec4ddf9efdbf317b12fedc,

title = "IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis",

abstract = "Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.",

author = "Macey, {Matthew R.} and Sturgill, {Jamie L.} and Morales, {Johanna K.} and Falanga, {Yves T.} and Joshua Morales and Norton, {Sarah K.} and Nitin Yerram and Hoon Shim and Josephine Fernando and Gifillan, {Alasdair M.} and Gregorio Gomez and Lawrence Schwartz and Carole Oskeritzian and Sarah Spiegel and Daniel Conrad and Ryan, {John J.}",

year = "2010",

month = may,

day = "1",

doi = "10.4049/jimmunol.0903477",

language = "English",

volume = "184",

pages = "4688--4695",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "9",

}

Macey, MR, Sturgill, JL, Morales, JK, Falanga, YT, Morales, J, Norton, SK, Yerram, N, Shim, H, Fernando, J, Gifillan, AM, Gomez, G, Schwartz, L, Oskeritzian, C, Spiegel, S, Conrad, D & Ryan, JJ 2010, 'IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis', Journal of Immunology, vol. 184, no. 9, pp. 4688-4695. https://doi.org/10.4049/jimmunol.0903477

TY - JOUR

T1 - IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis

AU - Macey, Matthew R.

AU - Sturgill, Jamie L.

AU - Morales, Johanna K.

AU - Falanga, Yves T.

AU - Morales, Joshua

AU - Norton, Sarah K.

AU - Yerram, Nitin

AU - Shim, Hoon

AU - Fernando, Josephine

AU - Gifillan, Alasdair M.

AU - Gomez, Gregorio

AU - Schwartz, Lawrence

AU - Oskeritzian, Carole

AU - Spiegel, Sarah

AU - Conrad, Daniel

AU - Ryan, John J.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.

AB - Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.

UR - http://www.scopus.com/inward/record.url?scp=77954468083&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0903477

DO - 10.4049/jimmunol.0903477

M3 - Article

C2 - 20304823

SN - 0022-1767

VL - 184

SP - 4688

EP - 4695

JO - Journal of Immunology

JF - Journal of Immunology

IS - 9

ER -

IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this