Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis

Yasuhiro Nemoto, Takanori Kanai, Shuji Tohda, Teruji Totsuka, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Tetsuya Fukuda, Osamu Miura, Hideo Yagita, Mamoru Watanabe

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Chronic inflammatory diseases are characterized by massive infiltration of innate and acquired immune cells in inflammatory sites. However, it remains unclear how these cells cooperate in the development of disease. Although bone marrow (BM) is a primary site for hematopoiesis of immune cells except T cells, BM recruits memory T cells from the periphery. We have recently demonstrated that colitogenic CD4+ memory T cells reside in BM of colitic CD4+CD45RBhigh T-cell-transferred SCID mice. Based on this background we here investigate whether granulocytes promote or suppress the expansion of colitogenic CD4+ T cells. Methods: First, we show that Gr-1highCD11b+ granulocytes were significantly increased in colitic BM along with a significant increase of peripheral granulocytes. Consistently, the colony-forming unit (CFU) assay revealed that granulocyte colony formation was dominantly induced by supernatants from anti-CD3-stimulated colitic BM CD4+ T cells. Results: Administration of granulocyte-depleting anti-Gr-1 mAb to colitic mice did not ameliorate the colitis, but exacerbated the wasting disease with an increased expansion of systemic, but not lamina propria, CD4+ T cells with activated phenotype. Conclusions: These results suggest that the increased granulopoiesis by colitogenic BM CD4+ T cells represent a negative feedback mechanism to control systemic inflammation.

Original languageEnglish
Pages (from-to)1491-1503
Number of pages13
JournalInflammatory bowel diseases
Volume14
Issue number11
DOIs
Publication statusPublished - 2008

Keywords

  • Bone marrow
  • CD4 T cells
  • Granulocytes
  • Immune regulation
  • Immunopathology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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    Nemoto, Y., Kanai, T., Tohda, S., Totsuka, T., Okamoto, R., Tsuchiya, K., Nakamura, T., Sakamoto, N., Fukuda, T., Miura, O., Yagita, H., & Watanabe, M. (2008). Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis. Inflammatory bowel diseases, 14(11), 1491-1503. https://doi.org/10.1002/ibd.20531