Eye‐mediated immune tolerance to Type II collagen in arthritis‐prone strains of mice

Farooq, Shukkur M.; Kumar, Ashok

doi:10.1111/jcmm.12376

Cited by 32 publications

(24 citation statements)

References 26 publications

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“…Nowadays, other routes are under evaluation in order to develop oral tolerance strategies for immunotherapy. In this sense, eye-induced tolerance is a promising therapeutic tool in the treatment of complicated autoimmune diseases such as CIA [37,38] or EAE [39–41]. Several tolerance protocols are being proposed for controlling inflammatory manifestations, in particular autoimmune diseases such as colitis [42–48].…”

Section: Resultsmentioning

confidence: 99%

Oral Tolerance Induced by OVA Intake Ameliorates TNBS-Induced Colitis in Mice

et al. 2017

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IntroductionLiterature data have shown that the consumption of dietary proteins may cause modulatory effects on the host immune system, process denominated oral tolerance by bystander suppression. It has been shown that the bystander suppression induced by dietary proteins can improve inflammatory diseases such as experimental arthritis. Here, we evaluated the effects of oral tolerance induced by ingestion of ovalbumin (OVA) on TNBS-induced colitis in mice, an experimental model for human Crohn’s disease.Methods and ResultsColitis was induced in BALB/c mice by instilling a single dose of TNBS (100 mg/kg) in ethanol into the colon. Tolerized mice received OVA (4mg/mL) dissolved in the drinking water for seven consecutive days, prior to or concomitantly with the intrarectal instillation. Control groups received protein-free water and ethanol by intrarectal route. We observed that either the prior or concomitant induction of oral tolerance were able to reduce the severity of colitis as noted by recovery of body weight gain, improvement of clinical signs and reduction of histological abnormalities. The in vitro proliferation of spleen cells from tolerant colitic mice was lower than that of control mice, the same as the frequencies of CD4+ T cells secreting IL-17 and IFN-γ. The frequencies of regulatory T cells and T cells secreting IL-10 have increased significantly in mice orally treated with OVA. The levels of inflammatory cytokines (IL-17A, TNF-α, IL-6 and IFN-γ) were lower in supernatants of cells from tolerant colitic mice, whereas IL-10 levels were higher.ConclusionOur data show that the modulation of immune response induced by oral tolerance reduces the severity of experimental colitis. Such modulation may be partially attributed to the increase of Treg cells and reduction of pro-inflammatory cytokines in peripheral lymphoid organs of tolerant mice by bystander suppression.

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Section: Resultsmentioning

confidence: 99%

Oral Tolerance Induced by OVA Intake Ameliorates TNBS-Induced Colitis in Mice

et al. 2017

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“…36 Furthermore, it has been reported that the induction of antigen-specific peripheral immune tolerance in CIA by injecting collagen type II in the immune-privileged site of the anterior eye chamber resulted in generation of Treg cells mediated via suppressive macrophages. 37 Whether such a Treg cell inducing mechanism via interaction with suppressive myeloid cells also underlies the therapeutic scheme of specific TNFR2 activation remains to be tested, for example, by the use of mice with cell-type-specific deletion of TNFR2. Thus the interaction between TNF and functionally active suppressor cells, such as MDSCs and Treg cells, seems to have a critical role in patients with chronic inflammation exerting seemingly paradoxical effects: TNF is a prototypical inflammatory mediator while, at the same time, it supports the resolution of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of TNF receptor type 2 expands regulatory T cells and ameliorates established collagen-induced arthritis in mice

et al. 2018

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Tumor necrosis factor (TNF) and its receptors TNF receptor type 1 (TNFR1) and type 2 (TNFR2) have a central role in chronic inflammatory diseases. While TNFR1 mainly confers inflammation, activation of TNFR2 elicits not only pro-inflammatory but also anti-inflammatory effects. In this study, we wanted to investigate the anti-inflammatory therapeutic potential of selective activation of TNFR2 in mice with established collagen-induced arthritis. Mice with established arthritis induced by immunization with bovine collagen type II were treated with six injections of the TNFR2-specific agonist TNCscTNF80, given every second day. Two days after treatment cessation, the cell compositions of bone marrow, spleen and lymph nodes were analyzed. Mice were visually scored until day 30 after the start of therapy and the degree of joint inflammation was determined by histology. Treatment with TNCscTNF80 increased arthritis-induced myelopoiesis. Little effect was seen on the infiltration rate of inflammatory immature myeloid cells and on the reduction of lymphoid cells in secondary lymphoid organs. Upon treatment, frequency of regulatory T (Treg) cells in the CD4 T-cell population was increased in both spleen and inguinal lymph nodes. In addition, the expression of TNFR2 on Treg cells was enhanced. The clinical score started to improve 1 week after cessation treatment and remained lower 30 days after initiation of therapy. The histological score also revealed amelioration of joint inflammation in TNCscTNF80-treated versus control mice. Activation of TNFR2 might provide a suitable therapeutic strategy in autoimmune arthritis by increasing the numbers of regulatory cell types, in particular Treg cells, and by attenuation of arthritis.Cellular and Molecular Immunology advance online publication, 29 January 2018; doi:10.1038/cmi.2017.138.

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“…Researchers have reported that Type II collagen (CII) could induce peripheral immune tolerance via the generation of CD8 + Treg cells when CII is injected into the anterior chamber (AC) of the eye3031. Whether paroxetine and CII treatment shares common mechanisms need to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

Wang

et al. 2017

Sci Rep

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T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4+ helper T (Th) cell and CD8+ cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ naïve Th (Thnaive) and effector Tc (Tceff)/ naïve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX). In addition, both serum and synovial IL-1β, TNF-α and CX3CL1 expression was effectively inhibited in treated rats. In vitro assay confirmed that paroxetine inhibits CX3CL1-induced T cell migration through blocking the activity of GRK2. Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. This study elucidates that paroxetine attenuates the symptoms of CIA rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway.

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Eye‐mediated immune tolerance to Type II collagen in arthritis‐prone strains of mice

Cited by 32 publications

References 26 publications

Oral Tolerance Induced by OVA Intake Ameliorates TNBS-Induced Colitis in Mice

Oral Tolerance Induced by OVA Intake Ameliorates TNBS-Induced Colitis in Mice

Stimulation of TNF receptor type 2 expands regulatory T cells and ameliorates established collagen-induced arthritis in mice

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

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