Macrophage polarization toward M1 phenotype in T cell transfer colitis model

Shin Ebihara; Toshiki Urashima; Wataru Amano; Hideto Yamamura; Noriko Konishi

doi:10.1186/s12876-023-03054-1

Macrophage polarization toward M1 phenotype in T cell transfer colitis model

BMC Gastroenterol. 2023 Nov 27;23(1):411. doi: 10.1186/s12876-023-03054-1.

Authors

Shin Ebihara¹, Toshiki Urashima², Wataru Amano², Hideto Yamamura², Noriko Konishi²

Affiliations

¹ Biological/Pharmacological Research Laboratories, Takatsuki Research Center, Central Pharmaceutical Research Institute, Japan Tobacco, Inc, 1-1 Murasaki-cho, Takatsuki, Osaka, 569-1125, Japan. shin.ebihara@jt.com.
² Biological/Pharmacological Research Laboratories, Takatsuki Research Center, Central Pharmaceutical Research Institute, Japan Tobacco, Inc, 1-1 Murasaki-cho, Takatsuki, Osaka, 569-1125, Japan.

Abstract

Background: T cell transfer colitis model is often used to study the CD4⁺ T cell functions in the intestine. However, the specific roles of macrophages in colitis remain unclear. In this study, we aimed to evaluate the phenotype and functions of macrophages in the colonic lamina propria (LP) in a colitis model.

Methods: Colitis was induced in scid mice via the adaptive transfer of CD4⁺CD45RB^hi T cells. Then, flow cytometry was used to determine the number of macrophages in the colonic LP and expression of cytokines in macrophages at the onset of colitis. Moreover, M1/M2 macrophage markers were detected in the colonic LP during colitis development using high-dimensional single-cell data and gating-based analyses. Expression levels of M1 markers in macrophages isolated from the colonic LP were measured using quantitative reverse transcription-polymerase chain reaction. Additionally, macrophages were co-cultured with T cells isolated from the colon to assess colitogenic T cell activation.

Results: Infiltration of macrophages into the colon increased with the development of colitis in the T cell transfer colitis model. M1/M2 macrophage markers were observed in this model, as observed in the colon of patients with inflammatory bowel disease (IBD). Moreover, number of M1 macrophages increased, whereas that of M2 macrophages decreased in the colonic LP during colitis development. M1 macrophages were identified as the main source of inflammatory cytokine production, and colitogenic T cells were activated via interactions with these macrophages.

Conclusions: Our findings revealed that macrophages polarized toward the M1 phenotype in LP during colitis development in the T cell transfer colitis model. Therefore, the colitis model is suitable for the evaluation of the efficacy of macrophage-targeted drugs in human IBD treatment. Furthermore, this model can be used to elucidate the in vivo functions of macrophages in the colon of patients with IBD.

Keywords: M1/M2 markers; Macrophage; T cell transfer colitis model.

MeSH terms

Animals
Colitis* / chemically induced
Colitis* / drug therapy
Humans
Inflammatory Bowel Diseases* / drug therapy
Macrophages
Mice
Phenotype
T-Lymphocytes