Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis

Keiichiro Saigusa, Tadakazu Hisamatsu, Tango Handa, Tomohisa Sujino, Yohei Mikami, Atsushi Hayashi, Shinta Mizuno, Kozue Takeshita, Toshiro Sato, Katsuyoshi Matsuoka, Takanori Kanai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Both Th1 and Th17 cell types are involved in the pathogenesis of chronic intestinal inflammation. We recently demonstrated that retinoid-related orphan receptor gamma t (RORγt)-expressing Th17 cells are progenitor cells for alternative Th1 cells, which have the potential to induce colitis. However, the involvement of classical Th1 (cTh1) cells generated directly from naive T cells without RORγt expression in the pathogenesis of colitis remains poorly understood. Methods: We performed a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of splenic CD4+CD45RBhigh T cells obtained from wild-type, RORγt<sup>gfp/gfp</sup>, or RORγt<sup>gfp/+</sup> mice into RAG-2<sup>-/-</sup> mice. Results: RAG-2<sup>-/-</sup> mice receiving transfer of in vitro-manipulated RORγt<sup>gfp/gfp</sup> Th1 cells developed colitis. RAG-2<sup>-/-</sup> mice co-transferred with splenic CD4+CD45RB<sup>high</sup> T cells obtained from wild-type mice and RORγt<sup>gfp/gfp</sup> mice developed colitis with a significant increase in RORγt<sup>gfp/gfp</sup> cTh1 cell numbers when compared with noncolitic mice transferred with splenic CD4+CD45RB<sup>high</sup> T cells obtained from RORγt<sup>gfp/gfp</sup> mice. Furthermore, RAG-2<sup>-/-</sup> mice transferred with in vivo-manipulated RORγt<sup>gfp/gfp</sup> cTh1 cells developed colitis with a significant increase in RORγt<sup>gfp/gfp</sup> cTh1 cell numbers. Conclusions: These findings indicate that both alternative Th1 cells and cTh1 cells have the potential to be colitogenic in an adaptive transfer model. The development of cTh1 cells was dependent on the co-existence of RORγt-expressing T cells, suggesting a critical role for the interactions of these cell types in the development of chronic intestinal inflammation.

Original languageEnglish
Pages (from-to)1820-1827
Number of pages8
JournalInflammatory Bowel Diseases
Volume20
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

Fingerprint

Th1 Cells
Colitis
T-Lymphocytes
Th17 Cells
Cell Count
Inflammation
Adoptive Transfer
Retinoids
Cell Communication
Stem Cells

Keywords

  • Alternative Th1
  • CD4+CD45RB<sup>high</sup> T cell
  • Classical Th1
  • Colitis
  • RORγt

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis. / Saigusa, Keiichiro; Hisamatsu, Tadakazu; Handa, Tango; Sujino, Tomohisa; Mikami, Yohei; Hayashi, Atsushi; Mizuno, Shinta; Takeshita, Kozue; Sato, Toshiro; Matsuoka, Katsuyoshi; Kanai, Takanori.

In: Inflammatory Bowel Diseases, Vol. 20, No. 10, 01.10.2014, p. 1820-1827.

Research output: Contribution to journalArticle

Saigusa, K, Hisamatsu, T, Handa, T, Sujino, T, Mikami, Y, Hayashi, A, Mizuno, S, Takeshita, K, Sato, T, Matsuoka, K & Kanai, T 2014, 'Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis', Inflammatory Bowel Diseases, vol. 20, no. 10, pp. 1820-1827. https://doi.org/10.1097/MIB.0000000000000149
Saigusa, Keiichiro ; Hisamatsu, Tadakazu ; Handa, Tango ; Sujino, Tomohisa ; Mikami, Yohei ; Hayashi, Atsushi ; Mizuno, Shinta ; Takeshita, Kozue ; Sato, Toshiro ; Matsuoka, Katsuyoshi ; Kanai, Takanori. / Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis. In: Inflammatory Bowel Diseases. 2014 ; Vol. 20, No. 10. pp. 1820-1827.
@article{c68735262ca34c109a05e24e3699b453,
title = "Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis",
abstract = "Background: Both Th1 and Th17 cell types are involved in the pathogenesis of chronic intestinal inflammation. We recently demonstrated that retinoid-related orphan receptor gamma t (RORγt)-expressing Th17 cells are progenitor cells for alternative Th1 cells, which have the potential to induce colitis. However, the involvement of classical Th1 (cTh1) cells generated directly from naive T cells without RORγt expression in the pathogenesis of colitis remains poorly understood. Methods: We performed a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of splenic CD4+CD45RBhigh T cells obtained from wild-type, RORγtgfp/gfp, or RORγtgfp/+ mice into RAG-2-/- mice. Results: RAG-2-/- mice receiving transfer of in vitro-manipulated RORγtgfp/gfp Th1 cells developed colitis. RAG-2-/- mice co-transferred with splenic CD4+CD45RBhigh T cells obtained from wild-type mice and RORγtgfp/gfp mice developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers when compared with noncolitic mice transferred with splenic CD4+CD45RBhigh T cells obtained from RORγtgfp/gfp mice. Furthermore, RAG-2-/- mice transferred with in vivo-manipulated RORγtgfp/gfp cTh1 cells developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers. Conclusions: These findings indicate that both alternative Th1 cells and cTh1 cells have the potential to be colitogenic in an adaptive transfer model. The development of cTh1 cells was dependent on the co-existence of RORγt-expressing T cells, suggesting a critical role for the interactions of these cell types in the development of chronic intestinal inflammation.",
keywords = "Alternative Th1, CD4+CD45RB<sup>high</sup> T cell, Classical Th1, Colitis, RORγt",
author = "Keiichiro Saigusa and Tadakazu Hisamatsu and Tango Handa and Tomohisa Sujino and Yohei Mikami and Atsushi Hayashi and Shinta Mizuno and Kozue Takeshita and Toshiro Sato and Katsuyoshi Matsuoka and Takanori Kanai",
year = "2014",
month = "10",
day = "1",
doi = "10.1097/MIB.0000000000000149",
language = "English",
volume = "20",
pages = "1820--1827",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis

AU - Saigusa, Keiichiro

AU - Hisamatsu, Tadakazu

AU - Handa, Tango

AU - Sujino, Tomohisa

AU - Mikami, Yohei

AU - Hayashi, Atsushi

AU - Mizuno, Shinta

AU - Takeshita, Kozue

AU - Sato, Toshiro

AU - Matsuoka, Katsuyoshi

AU - Kanai, Takanori

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Background: Both Th1 and Th17 cell types are involved in the pathogenesis of chronic intestinal inflammation. We recently demonstrated that retinoid-related orphan receptor gamma t (RORγt)-expressing Th17 cells are progenitor cells for alternative Th1 cells, which have the potential to induce colitis. However, the involvement of classical Th1 (cTh1) cells generated directly from naive T cells without RORγt expression in the pathogenesis of colitis remains poorly understood. Methods: We performed a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of splenic CD4+CD45RBhigh T cells obtained from wild-type, RORγtgfp/gfp, or RORγtgfp/+ mice into RAG-2-/- mice. Results: RAG-2-/- mice receiving transfer of in vitro-manipulated RORγtgfp/gfp Th1 cells developed colitis. RAG-2-/- mice co-transferred with splenic CD4+CD45RBhigh T cells obtained from wild-type mice and RORγtgfp/gfp mice developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers when compared with noncolitic mice transferred with splenic CD4+CD45RBhigh T cells obtained from RORγtgfp/gfp mice. Furthermore, RAG-2-/- mice transferred with in vivo-manipulated RORγtgfp/gfp cTh1 cells developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers. Conclusions: These findings indicate that both alternative Th1 cells and cTh1 cells have the potential to be colitogenic in an adaptive transfer model. The development of cTh1 cells was dependent on the co-existence of RORγt-expressing T cells, suggesting a critical role for the interactions of these cell types in the development of chronic intestinal inflammation.

AB - Background: Both Th1 and Th17 cell types are involved in the pathogenesis of chronic intestinal inflammation. We recently demonstrated that retinoid-related orphan receptor gamma t (RORγt)-expressing Th17 cells are progenitor cells for alternative Th1 cells, which have the potential to induce colitis. However, the involvement of classical Th1 (cTh1) cells generated directly from naive T cells without RORγt expression in the pathogenesis of colitis remains poorly understood. Methods: We performed a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of splenic CD4+CD45RBhigh T cells obtained from wild-type, RORγtgfp/gfp, or RORγtgfp/+ mice into RAG-2-/- mice. Results: RAG-2-/- mice receiving transfer of in vitro-manipulated RORγtgfp/gfp Th1 cells developed colitis. RAG-2-/- mice co-transferred with splenic CD4+CD45RBhigh T cells obtained from wild-type mice and RORγtgfp/gfp mice developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers when compared with noncolitic mice transferred with splenic CD4+CD45RBhigh T cells obtained from RORγtgfp/gfp mice. Furthermore, RAG-2-/- mice transferred with in vivo-manipulated RORγtgfp/gfp cTh1 cells developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers. Conclusions: These findings indicate that both alternative Th1 cells and cTh1 cells have the potential to be colitogenic in an adaptive transfer model. The development of cTh1 cells was dependent on the co-existence of RORγt-expressing T cells, suggesting a critical role for the interactions of these cell types in the development of chronic intestinal inflammation.

KW - Alternative Th1

KW - CD4+CD45RB<sup>high</sup> T cell

KW - Classical Th1

KW - Colitis

KW - RORγt

UR - http://www.scopus.com/inward/record.url?scp=84925815225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925815225&partnerID=8YFLogxK

U2 - 10.1097/MIB.0000000000000149

DO - 10.1097/MIB.0000000000000149

M3 - Article

VL - 20

SP - 1820

EP - 1827

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 10

ER -