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 163 publications

(144 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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“…GM-CSF exhibits pleiotropic activities on multiple cell types and is considered as an inflammatory as well as an anti-inflammatory molecule [38, 39]. Similar to the effect of HO-1, GM-CSF promotes tolerogenic DC differentiation and subsequent adaptive Treg differentiation [40].…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3+ Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models

et al. 2016

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Dendritic cells (DCs) are critical for instructing immune responses toward inflammatory or anti-inflammatory status. Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation. HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear. In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3+ regulatory T cells (Treg) differentiation in vitro and in vivo. Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation. This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.

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

Cited by 163 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

Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3+ Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models

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

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