IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

Abstract

IL-10 is a pleiotropic cytokine with stimulatory and inhibitory properties, and is thought to have a protective role in rheumatoid arthritis and collagen-induced arthritis (CIA). In this study, we investigated how IL-10 deficiency affects CIA and anti-collagen type II (CII) Ab-transferred arthritis in C57BL/10.Q (B10.Q) mice. The B10.Q.IL-10−/− mice had an 8-cM 129/Ola fragment around the IL-10 gene. The mice were treated with antibiotics, appeared healthy, and had no colitis. T cells from IL-10−/− mice expressed similar levels of IFN-γ, IL-2, and IL-4 after mitogen stimulation; however, macrophages showed a reduced TNF-α production compared with IL-10+/− littermates. IL-10−/− mice had an increased incidence, and a more severe CIA disease than the IL-10+/− littermates. To study the role of IL-10 in T cell tolerance, IL-10−/− were crossed into mice carrying the immunodominant epitope, CII(256–270), in cartilage (MMC) or in skin (TSC). Both IL-10−/− and IL-10+/− MMC and TSC mice were completely tolerized against CIA, indicating that lack of IL-10 in this context did not break tolerance. To investigate whether IL-10 was important in the effector phase of CIA, arthritis was induced with anti-CII Abs. Surprisingly, IL-10−/− were less susceptible to Ab-transferred arthritis, as only 30% showed signs of disease compared with 90% of the littermates. Therefore, IL-10 seemed to have a protective role in CIA, but seemed to exacerbate the arthritogenicity of anti-CII Abs. These data emphasize the importance of studying IL-10 in a defined genetic context in vivo, to understand its role in a complex disease like arthritis.

Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells

“…The blockade of IL-10 at the time AC were given restored the anti-CII antibody response to normal levels and abrogated protection from CIA. In contrast to published data (19,20) we did not see an exacerbation of arthritis as has been reported in IL-10-deficient mice. This may reflect that fact that blocking anti-IL-10 was given only during the induction phase of arthritis and not during the effector phase.…”

Lactobacillus helveticus suppresses experimental rheumatoid arthritis by reducing inflammatory T cell responses

“…Enhanced IL-10 expression inhibits pro-inflammatory immune responses and exerts protective effect against CIA progression (Johansson, Hansson, Nandakumar, Bäcklund, & Holmdahl, 2001;Tao et al, 2011). Indeed, administration of L. helveticus HY7801 significantly enhanced IL-10+ populations in total cells of dLN (upper plots in Fig.…”

Comment on "The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease"

“…That difference, however, is unlikely to explain the observed discrepancy. The OPN Ϫ/Ϫ 129/B6 mice also had a dramatic reduction of acute inflammation induced by monoclonal anti-type II collagen antibodies compared with OPN wt 129/B6 in experiments by Yumoto et al (8), which used a model very similar to the arthritis induced in our mice (12). This is important, because this model is an acute inflammation but is not dependent on T or B cells.…”

“…The flaw in these data is that they may be explained by linked polymorphic genes, because the mice were not fully backcrossed and typed in these experiments. We have deleted the OPN gene using homologous recombination of strain 129 -derived cells, and have subsequently backcrossed it to the C57/BL10 strain with a congenic major histocompatibility complex (MHC) fragment of the q haplotype (B10.Q), which is usually susceptible to EAE, collagen induced arthritis (CIA), and anti-CII antibody transfer induced arthritis (CAIA) (10)(11)(12). The gene was shown to be completely inactivated, with no aberrant transcript.…”