Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses

Interferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome

Toxic shock syndrome (TSS) caused by the superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes is characterized by robust T cell activation, profound elevation in systemic levels of multiple cytokines, including interferon-γ (IFN-γ), followed by multiple organ dysfunction and often death. As IFN-γ possesses pro- as well as anti-inflammatory properties, we delineated its role in the pathogenesis of TSS. Antibody-mediated in vivo neutralization of IFN-γ or targeted disruption of IFN-γ gene conferred significant protection from lethal TSS in HLA-DR3 transgenic mice. Following systemic high dose SEB challenge, whereas the HLA-DR3.IFN-γ+/+ mice became sick and succumbed to TSS, HLA-DR3.IFN-γ−/− mice appeared healthy and were significantly protected from SEB-induced lethality. SEB-induced systemic cytokine storm was significantly blunted in HLA-DR3.IFN-γ−/− transgenic mice. Serum concentrations of several cytokines (IL-4, IL-10, IL-12p40 and IL-17) and chemokines (KC, rantes, eotaxin and MCP-1) were significantly lower in HLA-DR3.IFN-γ−/− transgenic mice. However, SEB-induced T cell expansion in the spleens was unaffected and expansion of SEB-reactive TCR Vβ8+ CD4+ and CD8+ T cells was even more pronounced in HLA-DR3.IFN-γ−/− transgenic mice when compared to HLA-DR3.IFN-γ+/+ mice. A systematic histopathological examination of several vital organs revealed that both HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice displayed comparable severe inflammatory changes in lungs, and liver during TSS. Remarkably, whereas the small intestines from HLA-DR3.IFN-γ+/+ transgenic mice displayed significant pathological changes during TSS, the architecture of small intestines in HLA-DR3.IFN-γ−/− transgenic mice was preserved. In concordance with these histopathological changes, the gut permeability to macromolecules was dramatically increased in HLA-DR3.IFN-γ+/+ but not HLA-DR3.IFN-γ−/− mice during TSS. Overall, IFN-γ seemed to play a lethal role in the immunopathogenesis of TSS by inflicting fatal small bowel pathology. Our study thus identifies the important role for IFN-γ in TSS

Blockade of IFN-gamma does not affect the arthritogenicity of T cells generated during the induction of adjuvant arthritis but exacerbates the polyarthritis produced by adoptive transfer of arthritogenic effector cells

© 2007 Australasian Society for ImmunologyIFN- production is prominent in some models of autoimmune disease, including adjuvant arthritis (AA), but the role of IFN- in the pathogenesis of these diseases is uncertain. Experimental manipulation (administration of cytokine, blocking cytokine action with specific antibody, disruption of genes encoding the cytokine or its receptor) has revealed both pro- and anti-inflammatory effects, depending on the nature of the manipulation and the timing of the treatment. We examined separately the effects of cytokine blockade during the afferent and efferent phases of AA in Dark Agouti rats, using an adoptive transfer system. Effects of IFN- on the efferent phase were investigated by treating recipients with mAb DB-1, which blocks the activity of rat IFN-. When treatment was commenced before cell transfer, the resulting polyarthritis was more severe than in controls treated with normal IgG. Commencing treatment after the adoptively transferred disease had become established caused neither amelioration nor exacerbation, but did cause some delay in resolution. In contrast, treatment of donors did not appear to affect the generation of arthritogenic cells. The main effect of IFN- appears to be modulation of the arthritogenicity of the migratory effector T cells that can transfer AA

Book review: Power shift: the global political economy of energy transitions by Peter Newell

In Power Shift: The Global Political Economy of Energy Transitions, Peter Newell examines energy transitions at all levels of governance, drawing out the lessons learned from prior energy transitions to unlock an actionable understanding of today’s struggle to decarbonise the global economy. While the book stops short of presenting a detailed comparative analytical framework, researchers can learn a great deal from Newell’s activism, insights and his extensive survey of the existing literature, writes Mark S. Langevin. Power Shift: The Global Political Economy of Energy Transitions. Peter Newell. Cambridge University Press. 2021