GM-CSF: An immune modulatory cytokine that can suppress autoimmunity

Bhattacharya, Palash; Thiruppathi, Muthusamy; Elshabrawy, Hatem A.; Alharshawi, Khaled; Kumar, Prabhakaran; Prabhakar, Bellur S.

doi:10.1016/j.cyto.2015.05.030

Cited by 155 publications

(136 citation statements)

References 191 publications

(179 reference statements)

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“…GM-CSF-mediated inflammation has been implicated in some types of autoimmune diseases, including RA24. However, literatures also reveal that in many situations GM-CSF can act as an anti-inflammatory cytokine25. Low-dose GM-CSF induces tolerogenic DCs, and then selective promotes Treg cell expansion26.…”

Section: Discussionmentioning

confidence: 99%

IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

Liú

Cao²,

Wang

et al. 2016

Sci Rep

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IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+ T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.

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Section: Discussionmentioning

confidence: 99%

IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

Liú

Cao²,

Wang

et al. 2016

Sci Rep

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“…Other agents targeting IL-6/IL-6R are being developed and would offer potential efficacy in MG. GM-CSF is a cytokine acting as an important hematopoietic growth factor and immune modulator that has a profound effect on various circulating immune cells. Its effects on dendritic cell maturation and the enhancement of Treg function have been studied in the context of various autoimmune models [140]. GM-CSF has been shown to ameliorate experimental MG [141][142][143], and to enhance the in vitro suppressive function of isolated Tregs from patients with MG [144], possibly by upregulating FOXP3 expression in these cells.…”

Section: Il-6mentioning

confidence: 99%

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

2016

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Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

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“…Some cytokines, such as granulocyte macrophage colony stimulating factor (GM-CSF) can modulate DC towards a tolerogenic profile acting as an anti-inflammatory or regulatory modulator in autoimmune diseases, depending on its dose and the presence of other cytokines. Tolerogenic DCs can increase the frequency and function of regulatory T-cells [64–69]. …”

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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GM-CSF: An immune modulatory cytokine that can suppress autoimmunity

Cited by 155 publications

References 191 publications

IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

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

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