IL-10 mediates its biological activities through a heteromeric receptor complex composed of
the type II cytokine receptor subunits IL-10 R alpha and IL-10 R beta. IL-10 R alpha is a 110 kDa
transmembrane glycoprotein that is expressed on lymphocytes, NK cells, macrophages,
monocytes, astrocytes, intestinal epithelial cells, cytotrophoblasts, and activated hepatic
stellate cells (8-13), while the 75 kDa transmembrane IL-10 R beta is widely expressed (14, 15). The
IL-10 dimer binds to two IL-10 R alpha chains, triggering recruitment of two IL-10 R beta chains (14, 15).
IL-10 R beta does not bind IL-10 directly but is required for signal transduction. IL-10 R beta also
associates with IL-20 R alpha, IL-22 R alpha 1, or IL-28 R alpha to form the receptor complexes for IL-22, IL-26,
IL-28, and IL-29 (16-18).
The involvement of IL-10 in immunoregulation includes both suppressive and stimulatory
effects. It functions as an anti-inflammatory cytokine by inhibiting the expansion and
activation of Th1 cells and Th17 cells (19-21), and by promoting the development of M2
macrophages (21). Its expression by immunosuppressive regulatory T cells (Treg) and
regulatory B cells is important for Treg proliferation (19). Within a tumor microenvironment,
however, IL-10 inhibits the expansion of Treg as well as myeloid-derived suppressor cells (22,
23). IL-10 induces the intratumoral accumulation and activation of CD8+ T cells (24, 25). IL-10
exerts protective effects including limiting tissue damage in arthritic inflammation (19) and
promoting muscle regeneration after injury (21), but it also contributes to the persistence of
viral infections (26). The levels of IL-10 have been found to be elevated in Sjogren's syndrome
(saliva), primary CNS lymphoma (cerebrospinal fluid), and ovarian cancer (serum and ascites)
(27-29). Its levels have been found to be decreased in the serum of patients with recurrent
heart attacks or during preeclampsia and also in the seminal fluid of infertile men (30-32).
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