Enteric pathogens and gut function: Role of cytokines and STATs

Shea‐Donohue, Terez; Fasano, Alessio; Smith, Allen; Zhao, Aiping

doi:10.4161/gmic.1.5.13329

Cited by 34 publications

(28 citation statements)

References 91 publications

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“…mRNA expression of IL-17 was also not altered ( Figure 4B). Because type 2 T-cell responses require IL-4, STAT6, and GATA-3 expression, whereas type 1 T-cell responses depend on IL-12, STAT4, and T-bet, 29 mRNA expression of the transcription factors was determined in CD45.1 1 allogeneic T cells. STAT6 and GATA-3 mRNA expression was upregulated in the presence of MDSCs, whereas STAT4 and T-bet expression was unchanged ( Figure 4C).…”

Section: Mdsc Treatment Induces the Induction Of Type 2 T Cellsmentioning

confidence: 99%

In vitro-generated MDSCs prevent murine GVHD by inducing type 2 T cells without disabling antitumor cytotoxicity

Messmann¹,

Reisser²,

Leithäuser

et al. 2015

Blood

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Key Points• MDSC treatment prevents GVHD by skewing T cells toward type 2 T cells.• MDSCs proliferate in vivo, suppress independent of major histocompatibility complex class I expression, and do not impair allogeneic T-cell homing and the graft-versustumor effect.Myeloid-derived suppressor cells (MDSCs) inhibit T-cell expansion and functions by versatile mechanisms such as nutrient depletion, nitrosylation, or apoptosis. Since graftversus-host disease (GVHD) is characterized by the expansion of donor-derived T cells destroying recipient tissue, we analyzed whether MDSCs can be used for GVHD prevention in murine allogeneic bone marrow transplantation models. Transplantation of MDSCs, generated from bone marrow cells by granulocyte-macrophage colony-stimulating factor (GM-CSF)/G-CSF in vitro, inhibited GVHD-induced death and attenuated histologic GVHD, whereas antitumor cytotoxicity of alloantigen-specific T cells was maintained. MDSCs expanded in vivo and invaded lymphatic and GVHD target organs. Major histocompatibility complex class I expression on MDSCs was dispensable for their suppressive capacity. Inhibition of GVHD required the presence of MDSCs during T-cell priming, whereas allogeneic T-cell numbers and homing in lymphoid and GVHD target organs were not considerably affected in MDSC-treated mice. However, MDSCs skewed allogeneic T cells toward type 2 T cells upregulating T helper 2 (Th2)-specific cytokines. Type 2 T-cell induction was indispensable for GVHD prevention since MDSC treatment failed to prevent GVHD when allogeneic STAT6-deficient T cells, which are unable to differentiate into Th2 cells, were transplanted. MDSC-induced Th2 induction might be applicable for GVHD treatment in clinical settings. (Blood. 2015;126(9):1138-1148

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Section: Mdsc Treatment Induces the Induction Of Type 2 T Cellsmentioning

confidence: 99%

In vitro-generated MDSCs prevent murine GVHD by inducing type 2 T cells without disabling antitumor cytotoxicity

Messmann¹,

Reisser²,

Leithäuser

et al. 2015

Blood

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“…There are seven signal transducer and activator of transcription (STAT) family members and each STAT responds to specific cytokines leading to induction of gene expression. 36 Studies in H. bakeri-infected mice show that the upregulation of serpinB2 expression is dependent on STAT6, the transcription factor used exclusively by IL-4 and IL-13. Activation is tightly regulated and there is evidence also that proteases can regulate STAT6.…”

Section: Immune Regulation Of Serpinb2 Expressionmentioning

confidence: 99%

SerpinB2 mediated regulation of macrophage function during enteric infection

2014

Self Cite

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Host defense is an orchestrated response involving changes in the expression of receptors and release of mediators from both immune and structural cells. There is a growing recognition of the important role of proteolytic pathways for the protective immune response to enteric pathogens. Enteric nematode infection induces a type 2 immune response with polarization of macrophages toward the alternatively activated phenotype (M2). The Th2 cytokines, IL-4, and IL-13, induce a STAT6-dependent upregulation of the expression of the protease inhibitor, serpinB2, which protects macrophages from apoptosis. M2 are critical to worm clearance and a novel role for serpinB2 is its regulation of the chemokine, CCL2, which is necessary for monocyte and/or macrophage influx into small intestine during infection. There is a growing list of factors including immune (LPS, Th2 cytokines) as well as hormonal (gastrin, 5-HT) that are linked to increased expression of serpinB2. Thus, serpinB2 represents an immune regulated factor that has multiple roles in the intestinal mucosa.

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“…Cytokines [27] are quickly released to neighbors which will enhance the engulfing ability of the monocytes and macrophages and promote the lymphocytes to maturate effector cells. Although the macrophage is no longer a vehicle for transmitting pathogens to other cells it may be exposed to more potent bactericidal cells and the humoral immune system.…”

Section: Apoptosis and Immunementioning

confidence: 99%

Caspase work model during pathogen infection

Chang

2011

Virol. Sin.

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Caspases are an evolutionarily conserved family of aspartate-specific cystein-dependent proteases with essential functions in apoptosis and normally exist in cells as inactive proenzymes. In addition to the inflammatory caspases, the initiator and effector caspases have been shown to have an important role in regulating the immune response, but are involved in different ways. We give a brief introduction on the benefit of apoptosis on the clearance of invasive pathogens, and the caspase functions involved in the immune response. Then we construct a working model of caspases during pathogen invasion. A detailed description of the three modes is given in the discussion. These three modes are regulated by different inhibitors, and there may be a novel way to treat intracellular pathogen and autoimmune diseases based on the specific inhibitors.

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Enteric pathogens and gut function: Role of cytokines and STATs

Cited by 34 publications

References 91 publications

In vitro-generated MDSCs prevent murine GVHD by inducing type 2 T cells without disabling antitumor cytotoxicity

In vitro-generated MDSCs prevent murine GVHD by inducing type 2 T cells without disabling antitumor cytotoxicity

SerpinB2 mediated regulation of macrophage function during enteric infection

Caspase work model during pathogen infection

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