Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation

Silvia Piconese, Giorgia Gri, Claudio Tripodo, Silvia Musio, Andrea Gorzanelli, Barbara Frossi, Rosetta Pedotti, Carlo E. Pucillo, Mario P. Colombo

Research output: Contribution to journalArticle

Abstract

The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses.

Original languageEnglish
Pages (from-to)2639-2648
Number of pages10
JournalBlood
Volume114
Issue number13
DOIs
Publication statusPublished - 2009

Fingerprint

Th17 Cells
T-cells
Regulatory T-Lymphocytes
Mast Cells
Cell Differentiation
Interleukin-6
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Interleukin-17
Lymph Nodes
Cytokines
Molecules

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation. / Piconese, Silvia; Gri, Giorgia; Tripodo, Claudio; Musio, Silvia; Gorzanelli, Andrea; Frossi, Barbara; Pedotti, Rosetta; Pucillo, Carlo E.; Colombo, Mario P.

In: Blood, Vol. 114, No. 13, 2009, p. 2639-2648.

Research output: Contribution to journalArticle

Piconese, S, Gri, G, Tripodo, C, Musio, S, Gorzanelli, A, Frossi, B, Pedotti, R, Pucillo, CE & Colombo, MP 2009, 'Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation', Blood, vol. 114, no. 13, pp. 2639-2648. https://doi.org/10.1182/blood-2009-05-220004
Piconese, Silvia ; Gri, Giorgia ; Tripodo, Claudio ; Musio, Silvia ; Gorzanelli, Andrea ; Frossi, Barbara ; Pedotti, Rosetta ; Pucillo, Carlo E. ; Colombo, Mario P. / Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation. In: Blood. 2009 ; Vol. 114, No. 13. pp. 2639-2648.
@article{64491e85843e4a489c7968805e9acab4,
title = "Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation",
abstract = "The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses.",
author = "Silvia Piconese and Giorgia Gri and Claudio Tripodo and Silvia Musio and Andrea Gorzanelli and Barbara Frossi and Rosetta Pedotti and Pucillo, {Carlo E.} and Colombo, {Mario P.}",
year = "2009",
doi = "10.1182/blood-2009-05-220004",
language = "English",
volume = "114",
pages = "2639--2648",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "13",

}

TY - JOUR

T1 - Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation

AU - Piconese, Silvia

AU - Gri, Giorgia

AU - Tripodo, Claudio

AU - Musio, Silvia

AU - Gorzanelli, Andrea

AU - Frossi, Barbara

AU - Pedotti, Rosetta

AU - Pucillo, Carlo E.

AU - Colombo, Mario P.

PY - 2009

Y1 - 2009

N2 - The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses.

AB - The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses.

UR - http://www.scopus.com/inward/record.url?scp=70350492339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350492339&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-05-220004

DO - 10.1182/blood-2009-05-220004

M3 - Article

C2 - 19643985

AN - SCOPUS:70350492339

VL - 114

SP - 2639

EP - 2648

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -