Depletion of complement does not impact initiation of xenobiotic‐induced autoimmune disease

Cauvi, David M.; Toomey, Christopher B.; Pollard, K. Michael

doi:10.1111/j.1365-2567.2011.03545.x

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…Experimental CVF administration was once thought to directly stimulate T cells, but such effects were later attributed to mitogen contamination (Rumjanek et al, 1978; Cauvi et al, 2012). Because our disease models were T cell-dependent, we utilized highly-purified CVF from a commercial source for our studies.…”

Section: Discussionmentioning

confidence: 99%

Complement and CD4+ T cells drive context-specific corneal sensory neuropathy

Royer

Echegaray-Mendez

Lin

et al. 2019

eLife

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Whether complement dysregulation directly contributes to the pathogenesis of peripheral nervous system diseases, including sensory neuropathies, is unclear. We addressed this important question in a mouse model of ocular HSV-1 infection, where sensory nerve damage is a common clinical problem. Through genetic and pharmacologic targeting, we uncovered a central role for C3 in sensory nerve damage at the morphological and functional levels. Interestingly, CD4 T cells were central in facilitating this complement-mediated damage. This same C3/CD4 T cell axis triggered corneal sensory nerve damage in a mouse model of ocular graft-versus-host disease (GVHD). However, this was not the case in a T-dependent allergic eye disease (AED) model, suggesting that this inflammatory neuroimmune pathology is specific to certain disease etiologies. Collectively, these findings uncover a central role for complement in CD4 T cell-dependent corneal nerve damage in multiple disease settings and indicate the possibility for complement-targeted therapeutics to mitigate sensory neuropathies.

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Section: Discussionmentioning

confidence: 99%

Complement and CD4+ T cells drive context-specific corneal sensory neuropathy

Royer

Echegaray-Mendez

Lin

et al. 2019

eLife

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“…This response, however, could not be explained by increased T-cell activation but rather was explained by increased levels of IFN- γ , IL-2, IL-4, and IL-10 ( Table 2 ) [ 19 ]. Furthermore, depletion of C3 was found to have no major effects on development of mHgIA suggesting that the role of DAF1 in mHgIA is independent of an intact complement system [ 104 ]. This is supported by results showing that C3 levels are not affected following mercury exposure of mHgIA sensitive or resistant strains (Pollard, unpublished results).…”

Section: Daf In Animal Models Of Systemic Autoimmune Diseasementioning

confidence: 99%

“…Several models of systemic autoimmunity exhibit disease independent of an intact complement system, yet an exacerbated phenotype is observed by DAF1 deletion [ 19 , 21 , 76 , 104 , 105 ]. This suggests that complement-independent effects of DAF1 are the major contributors to tolerance induction via the interaction of DAF (CD55) with its natural ligand, CD97.…”

Section: How Does Daf1 Regulate Immune Tolerance?mentioning

confidence: 99%

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

Toomey

Cauvi

Pollard

2014

Autoimmune Diseases

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Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.

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“…This phenotype is characterized by hypersecretion of interferon (IFN)-γ and IL-2 as well as down-regulation of the inhibitory cytokine IL-10 during antigen restimulation of lymphocytes in vitro [19] . Furthermore, several studies have shown that the absence of Daf1 exacerbates disease in a variety of autoimmune models, including systemic autoimmune disease in the MLR-Faslpr mouse [20] , [21] , focal and segmental glomerulosclerosis [22] and mercury-induced autoimmunity [23] , by enhancing T-cell and autoimmune responses associated with hypersecretion of IFN-γ, IL-12 and IL-17 [19] , [24] , [25] , [26] .…”

Section: Introductionmentioning

confidence: 99%

Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

et al. 2014

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Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1−/− mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1−/− mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1−/− mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1−/− mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

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Depletion of complement does not impact initiation of xenobiotic‐induced autoimmune disease

Cited by 6 publications

References 49 publications

Complement and CD4+ T cells drive context-specific corneal sensory neuropathy

Complement and CD4+ T cells drive context-specific corneal sensory neuropathy

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

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