Regulatory T-cell stability and plasticity in mucosal and systemic immune systems.
Regulatory T cells (Treg) express the forkhead box p3 (Foxp3) transcription factor and suppress pathological immune responses against self and foreign antigens, including commensal microorganisms. Foxp3 has been proposed as a master key regulator for Treg, required for their differentiation, maintenance, and suppressive functions. Two types of Treg have been defined. Natural Treg (nTreg) are usually considered to be a separate sublineage arising during thymus differentiation. Induced Treg (iTreg) originate upon T cell receptor (TCR) stimulation in the presence of tumor growth factor beta. Although under homeostatic conditions most Treg in the periphery are nTreg, special immune challenges in the intestine promote more frequently the generation of iTreg. Furthermore, recent observations have challenged the notion that Treg are a stable sublineage, and they suggest that, particularly under lymphopenic and/or inflammatory conditions, Treg may lose Foxp3 and/or acquire diverse effector functions, especially in the intestine, which may contribute to uncontrolled inflammation.
Murai
M
M
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Krause
P
P
Cheroutre
H
H
Kronenberg
M
M
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D044127:Epigenesis, Genetic; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020506:Untranslated Regions / Q000235:genetics
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020506:Untranslated Regions