In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis.

IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33-treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33-treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39(high) Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development.

Personality modulates proportions of CD4+ regulatory and effector T cells in response to socially induced stress in a rodent of wild origin.

The way how individuals respond to chronic challenges can vary tremendously, and such differences are closely linked to personality. The few available studies on individual differences in stress-related immunosuppression in non-human mammals have been mainly carried out with laboratory strains. We conducted a study in male mound-building mice (Mus spicilegus) of wild origin. We distinguished between high (HAN) and low anxious/neophobic (LAN) personality types, quantified by subjects' consistent and associated behavioral responses in repeated elevated plus maze and novel object tests. After reaching maturity, parts of the subjects were regularly confronted to different resident pairs over a period of 5days to provoke a condition of chronic social stress, while others were used as untreated controls. We measured fecal corticosteroid metabolite (FCM) concentrations and different cellular immune parameters from blood and spleen. Socially confronted HAN showed higher increases in FCM concentrations than LAN, indicating a more pronounced physiological stress response in the former personality type. HAN of the experimental group also showed lower percentages of effector T cells (Teff) and higher regulatory T cells (Treg) in the spleen; the latter are known for their immunosuppressive activity. Considering the ratio of Teff/Treg, animals with higher increases in FCM concentrations during the late period of the experiment showed a stronger shift towards Treg cells, supporting immunosuppressive effects of chronically elevated corticosteroid levels. Summarizing, our results strongly suggest that immunomodulatory effects of socially induced stress were altered by individual differences in anxiety/neophobia, emphasizing the significance of personality in shaping physiological responses to challenge.