Foxp3 expressing regulatory T-cells in allergic disease.
Allergic diseases such as asthma, rhinitis and eczema are increasing in prevalence worldwide, in particular in industrialised countries affecting up to 20% of the population. Regulatory T-cells (Tregs) have been shown to be critical in T-cell homeostasis and in the maintenance of immune responses, such as prevention of autoimmunity and hampering allergic diseases. The so-called 'natural' CD4+CD25+ Tregs and/or IL-10-producing Tr1 cells have been shown to be responsible for the protection of immune tolerance and intact immune reactions following exposure to allergens such as aeroallergens or food allergens. In this regard, both cell-cell contact (through membrane bound TGF-beta or via suppressive molecules such as CLTA-4) and soluble cytokine-(TGF-beta and IL-10) dependent mechanisms have been shown to contribute to the ability of Tregs to operate effectively. The transcription factor Foxp3, a member of the forkhead-winged helix family, appears to be critical in the suppressive abilities of regulatory T-cells. Adoptive transfer of CD4+CD25+ Tregs from healthy to diseased animals corroborated and provided further evidence of the vital role of these populations in the prevention or cure of certain autoimmune conditions. Clinical improvement seen after allergen immunotherapy for allergic diseases such as rhinitis and asthma has also been associated with the induction of IL-10 and TGF-beta producing Trl cells as well as Foxp3 expressing CD4+CD25+ T-cells, resulting in the suppression ofTh2 cytokine milieu. Activation and expansion ofantigen-specific CD4+CD25+ Tregs in vivo using adjuvants such as IL-10 or pharmacological agents such as low dose steroids or vitamin D3 could represent novel approaches to induce antigen-specific tolerance in immune-mediated conditions such as allergic asthma, autoimmune disease and the rejection of transplanted organs in man.
Nouri-Aria
Kayhan T
KT
Department of Allergy and Clinical Immunology, National Heart and Lung Institute at Imperial College London, Exhibition Road, London SW7 2AZ, England, UK. k.nouri-aria@imperial.ac.uk
D000818:Animals; D001249:Asthma / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D012220:Rhinitis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors