IgG4-re lated tubulo interstitial ne phri tis (TIN) shows char acter is tic se rum IgG4 el e va tion and in creased IgG4-pos i tive plasma cells in the re nal interstitium, and in clu sion of TIN as an IgG4-related sys temic dis ease has been sug gested. IgG4 is the rar est IgG sub class and is a Th2-dependent isotype with low af fin ity for tar get an ti gen. Al though the pathogenesis of this dis ease has not been elu ci dated, pos i tive serum im mune com plex and hypo comple mentemia in some pa tients with this dis ease suggest that im mune com plex mech a nisms are in volved in the cau sa tion of this dis ease. We se lected 20 cases of histological di ag nosed TIN. These cases were eti o log ically dif fer ent and in cluded 4 cases of IgG4-related TIN. We ex tracted RNA from par af fin em bed ded biopsied kid ney and eval u ated expres sion lev els of var i ous cytokines for each case by real time PCR. Com par i son of cytokine pro duc tion pat terns among dif ferent dis ease-as so ci ated TINs re vealed that IgG4-re lated TIN ex hib ited a quite dis tinct pat tern. On the one hand, there was no ex pression of IL-2, IFN-γ, IL-17 and IL-6, whereas pro duc tion of IL-4, IL-10 and TGF-β was, on the other hand, re mark ably in creased in IgG4-related TIN. Based on these cytokine pro duc tion re sults, Th2 and Treg appear to play a cen tral role in IgG4-re lated TIN.