The balance of intestinal Foxp3⁺ regulatory T cells and Th17 cells and its biological significance

Abstract

Balanced mucosal immunity in the gut is critical for host homeostasis and defense. Th17 cells are a subset of IL-17-producing CD4⁺ T cells, which play a crucial role in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune diseases. CD4⁺CD25⁺ Foxp3⁺ regulatory T cells (Tregs) are recognized as one of the major regulatory factors in immune tolerance and inflammatory responses. Since both Tregs and Th17 cells pertain to the gut immune system, their inter-regulation and balance represent a novel mechanism for maintaining the intestinal immune and inflammatory homeostasis. Accordingly, the imbalance and dysregulation of Tregs and Th17 cells in the intestine is closely associated with intestinal autoimmune disorders like the inflammatory bowel diseases. In this review, we discuss the characteristics of gut Tregs and Th17 cells and their role in gut diseases.

Keywords::

• immune regulation
• intestine
• mucosal immunity
• Treg
• Th17

Acknowledgements

The authors appreciate D Corley and SE Zhang for kindly editing the manuscript.

Financial & competing interests disclosure

This work was supported by grants from the National Basic Research Program of China (2010CB945301, 2011CB710903), the National Natural Science Foundation for General and Key Programs (81000189 to J Du, C81130055, C81072396 to Y Zhao), and Knowledge Innovation Program of Chinese Academy of Sciences (XDA04020202-19). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Maintaining the homeostasis of the gut immune microenvironments is critical for host immune tolerance to food, self-antigens and parasites, while allowing efficient immune response to exogenous pathogenic microorganisms.

• Treg actively suppress effector cells and contribute to the maintenance of intestinal immune homeostasis. Disturbances in Treg number and function are closely associated with immune disorders in the gut.

• Th17 cells mainly exist in the intestine and protect vertebrates from exogenous pathogenic microorganisms through the recruitment of macrophages and neutrophils to infected tissues. To a lesser extent, Th17 cells also cause numerous intestinal diseases such as colitis and colorectal cancers.

• Retinoic acid cooperates with TGF-β1 to promote the differentiation of Treg in mesenteric lymph nodes and lamina propria. It is also capable of inducing Th17 cells under certain inflammatory conditions.

• Microorganisms in the gut considerably influence the intestinal immune homeostasis through controlling the induction of Th17 cells and/or Treg.

Notes