Enforced ROR(gamma)t expression in haematopoietic stem cells increases regulatory T cell number, which reduces immunoreactivity and attenuates hypersensitivity in vivo.

Abstract

BACKGROUND:

The retinoic acid receptor-related orphan receptor gammat (ROR(gamma)t) is a key transcription factor involved in the generation of T-helper 17 (Th17) cells, which mediate tissue inflammation and autoimmunity. However, recent studies indicated that less than half of all ROR(gamma)t(+) Talphabeta cells express IL-17, while the others are Foxp3(+) Talphabeta cells expressing IL-10. These observations raise questions regarding the role of ROR(gamma)t in the early differentiation process of T cells from haematopoietic stem cells.

METHODS:

To examine the role of RORyt in T cell differentiation, mice were reconstituted with ROR(gamma)t cDNA-transduced haematopoietic stem cells and the role of ROR(gamma)t in T cell differentiation was studied in a mouse bone marrow transplantation model in vivo.

RESULTS:

While the number of Th17 cells increased with the reduction in Thl cell number in transplanted mice, peripheral blood Foxp3(+) Talphabeta cell number also increased, which attenuated the severity of contact hypersensitivity on skin exposed to 2,4-dinitrofluorobenzene. The number of non-transduced Foxp3(+) regulatory T cells (Treg cells) also increased in these mice.

CONCLUSION:

These observations suggest that the enforced expression of ROR(gamma)t in haematopoietic stem cells induces differentiation of Thl7 cells and results in an increase in Foxp3(+) Treg cell number to limit self-tissue damage.

• Authors: Yasuhiro Fujisawa, Tsukasa Nabekura, Yasuhiro Kawachi, Fujio Otsuka, Masafumi Onodera
• Journal: Asian Pacific journal of allergy and immunology (Asian Pac J Allergy Immunol) Vol. 29 Issue 1 Pg. 86-93 (Mar 2011) ISSN: 0125-877X [Print] Thailand
• PMID: 21560493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Forkhead Transcription Factors
• Nuclear Receptor Subfamily 1, Group F, Member 3

Topics

• Animals
• Cell Differentiation (immunology)
• Cell Proliferation
• Forkhead Transcription Factors (immunology, metabolism)
• Gene Expression Regulation (immunology)
• Gene Order
• Genetic Vectors (genetics)
• HEK293 Cells
• Hematopoiesis (genetics)
• Hematopoietic Stem Cell Transplantation
• Hematopoietic Stem Cells (immunology)
• Humans
• Hypersensitivity (immunology)
• Jurkat Cells
• Mice
• Mice, Inbred C57BL
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, metabolism)
• Retroviridae (genetics)
• T-Lymphocytes, Regulatory (cytology, immunology)
• Th17 Cells (immunology, metabolism)