Allergy Asthma Immunol Res.  2017 Mar;9(2):107-115. 10.4168/aair.2017.9.2.107.

Role of Regulatory Cells in Oral Tolerance

• Wawrzyniak M
• O'Mahony L
• Akdis M

• KMID: 2413384
• DOI: http://doi.org/10.4168/aair.2017.9.2.107

Abstract

The immune system is continuously exposed to great amounts of different antigens from both food and intestinal microbes. Immune tolerance to these antigens is very important for intestinal and systemic immune homeostasis. Oral tolerance is a specific type of peripheral tolerance induced by exposure to antigen via the oral route. Investigations on the role of intestinal immune system in preventing hypersensitivity reactions to innocuous dietary and microbial antigens have been intensively performed during the last 2 decades. In this review article, we discuss how food allergens are recognized by the intestinal immune system and draw attention to the role of regulatory T (Treg) and B (Breg) cells in the establishment of oral tolerance and tolerogenic features of intestinal dendritic cells. We also emphasize the potential role of tonsils in oral tolerance induction because of their anatomical location, cellular composition, and possible usage to develop novel ways of specific immunotherapy for the treatment of allergic diseases.

Keyword

Food allergy; oral tolerance; regulatory cells; dendritic cells; Tregs

MeSH Terms

Allergens
Dendritic Cells
Food Hypersensitivity
Homeostasis
Hypersensitivity
Immune System
Immune Tolerance
Immunotherapy
Palatine Tonsil
Peripheral Tolerance
Allergens

Figure

• 

  Figure Role of regulatory cells in the induction of oral tolerance. Food antigens are acquired by the immune system via several different mechanisms. First of all, dendritic cells (DC) expressing CD11b and CX3CR1 extend dendritic processes between epithelial cells and sample antigens from lumen (1). As CX3CR1+CD11b+ DC do not express CCR7 or migrate to mesenteric lymph node, they mainly contribute to local, antigen-specific expansion of regulatory cells. Additionally, M cells localized in Payer's patches (2), intestinal cells via paracellular (3), or transcellular route (4), and goblet cells (5) might contribute to antigen sampling. Antigens are uptaken by CD11C+CD103+DC. DC expressing CD11c and CD103 co-express CCR7 and migrate to MLN under homeostatic conditions. In MLN produced by of TGF-beta, IL-10, RALDH, and IDO contribute to active promotion and development of Treg and Breg cells. Treg cells differentiated in MLN by CD11C+CD103+ DC up-regulate α4β7 integrin and CCR9 receptor that are responsible for T-cell homing from MLN to the lamina propria. In lamina propria, CD25-Foxp3--, IL-10-and TGF-β-producing Th3/Tr1 cells, CD25+Foxp3+ α4β7+CCR9+ iTreg cells, and IL-10+IgG4+ Breg cells suppress Th2-dependent allergic inflammation by decreasing mast cell activation, IL-4/IL-5/IL-13 production from ILC2 and Th2 cells, and IgE production from plasma cells.

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