부산대학교 도서관

Signaling through the TLR family of molecular pattern recognition receptors has been implicated in the induction of innate and adaptive immune responses. A role for TLR signaling in the maintenance and/or regulation of Treg function has been proposed, however its functional relevance remains unclear. Here we have shown that TLR9 is highly expressed by human Treg secreting the antiinflammatory cytokine IL-10 induced following stimulation of blood and tissue [CD3.sup.+] T cells in the presence of 1[alpha],25-dihydroxyvitamin D3 (1[alpha]25VitD3), the active form of Vitamin D, with or without the glucocorticoid dexamethasone. By contrast, TLR9 was not highly expressed by naturally occurring [CD4.sup.+][CD25.sup.+] Treg or by Th1 and Th2 effector cells. Induction of TLR9, but not other TLRs, was IL-10 dependent and primarily regulated by 1[alpha]25VitD3 in vitro. Furthermore, ingestion of calcitriol (1[alpha]25VitD3) by human volunteers led to an increase of both IL-10 and TLR9 expression by [CD3.sup.+][CD4.sup.+] T cells analyzed directly ex vivo. Stimulation of 1[alpha]25VitD3-induced IL-10-secreting Treg with TLR9 agonists, CpG oligonucleotides, resulted in decreased IL-10 and IFN-[gamma] synthesis and a concurrent loss of regulatory function, but, unexpectedly, increased IL-4 synthesis. We therefore suggest that TLR9 could be used to monitor and potentially modulate the function of 1[alpha]25VitD3-induced IL-10-secreting Treg in vivo, and that this has implications in cancer therapy and vaccine design.
Introduction The TLRs represent a family of evolutionarily conserved receptors, which recognize pathogen-associated molecular patterns (PAMPs) and certain host molecules. Ten TLRs (TLR1-10) have been identified in humans to date. [...]