Title: Erratum: Pattern on the antinuclear antibody–HEp‐2 test is a critical parameter for discriminating antinuclear antibody–positive healthy individuals and patients with autoimmune rheumatic diseases
Abstract: absence of IL-23, Th17 cells can be generated but are not fully differentiated and not sustained in vivo, and autoimmune inflammation is not sustained (7,8).In vivo, an initial TGF signal is required for generation of pathogenic Th17 cells and development of EAE, a mouse model of human MS (7,8).This was illustrated in experiments with local blockade of TGF and experiments using mice with transgenic expression of mutant TGF subunit receptor II in T cells (8).These data suggest that in vivo, both TGF and IL-23 are essential for the development of pathogenic Th17 cells and full-blown autoimmune disease.Wang and colleagues cite the findings reported by Ghoreschi et al (5) and argue for the more pathogenic effect of Th17( 23) cells (generated in vitro with IL-6 plus IL-1 and IL-23).Ghoreschi et al compared the capacity of Th17( 23) cells with that of Th17() cells (generated in vitro with IL-6 plus IL-1 and TGF) in an adoptive transfer model of EAE.It was concluded that Th17(23) cells are more pathogenic than Th17() cells.However, it must be noted that Th17() cells generated by IL-6, IL-1, and TGF- (with no addition of IL-23) might represent a not fully differentiated population of Th17 cells.EAE induced by these Th17() cells may represent the initial clinical phase of the disease.By addition of IL-23, these Th17() cells may be allowed to further differentiate into Th17(23)-like cells.In contrast, Th17(23) cells generated in vitro with the combination of IL-1, IL-6, and IL-23 may represent effector Th17 cells, and therefore EAE induced by these Th17(23) cells in the adoptive transfer study is more likely to represent the effector phase of the disease.As demonstrated by Veldhoen et al ( 8), chronic inflammation and IL-23 are needed for sustained EAE in the effector phase.Finally, as Wang and colleagues point out, data derived from the study of an EAE model may not be generalizable to arthritis models.A recent study by Mus et al ( 9) directly examined the role of IL-23 and TGF using the same model of experimental arthritis in DBA/1 mice as was used in our study.Our data are consistent with Mus and colleagues' finding that TGF plus IL-6 is a potent inducer of Th17 cells from naive CD4ϩ T cells.IL-23 augments the effect of TGF plus IL-6 on induction of Th17 cells (9).However, as demonstrated in previous studies (1,2), IL-23 alone has little effect on initiation of Th17 cell differentiation.TGF plus IL-6 increases IL-21 production by Th17 cells stimulated with type II collagen, and this is further amplified by .In vitro, TGF induces FoxP3 expression and promotes induced Treg (iTreg) cells.FoxP3 interacts with retinoic acid receptor-related orphan receptor ␥t to repress Th17 cell formation.Our study was focused on effects of TGF in the interphase between Th17 and iTreg cells.Our data suggest that the deviation in the response of DBA/1 mouse CD4ϩ T cells to TGF signaling favors Th17 cell formation, and this may contribute to the susceptibility of DBA/1 mice to collagen-induced arthritis.