Is IgA nephropathy induced by abnormalities of CD4+CD25+Treg cells in the tonsils?

Abstract

IgA nephropathy (IgAN) is characterized by the accumulation of IgA deposits, predominantly in the glomerular mesangium, and represents the most common form of glomerulonephritis. Much evidence showed that tonsils were closely related to IgAN. Urinary findings were deteriorated after tonsil stimulation in patients with IgAN. Tonsillectomy can improve the urinary findings, keep stable renal function, improve mesangial proliferation, decrease IgA deposits and have a favorable effect on long-term renal survival in some IgAN patients. Recent studies indicate that CD4(+)CD25(+) regulatory T cells (Treg) are of critical importance to the maintenance of tolerance by inhibiting the activation and proliferation of autoreactive T cells. Depletion of the minor CD4(+)CD25(+)Treg cells results in the development of organ-specific autoimmunity. Autoimmune diseases can be prevented by reconstitution of the animals with CD4(+)CD25(+)Treg cells. CD4(+)CD25(+)Treg cells are regulators in almost all of the animal models of human organ-specific diseases, transplant rejection and allergic diseases. Some patients with recurrent chronic tonsillitis have not suffered from renal disease, implying that it is possible to find a balance between immunity and tolerance. Some patients, however, suffered from IgAN along with recurrent chronic tonsillitis. It could be hypothesized that a numerical and/or functional deficit of CD4(+)CD25(+)Treg cells in the tonsils of IgAN patients might trigger the development of the diseases. If the hypothesis is correct, altering CD4(+)CD25(+)Treg cell numbers and/or enhancing CD4(+)CD25(+)Treg responses might be useful in the prevention and treatment of IgAN.