Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis by Regulating Th17/Treg Cell Balance

Zhang, Liya; Zhang, Yanjie; Zhong, Wenxiang; Di, Caixia; Lin, Xinhua; Xia, Zhenwei

doi:10.1074/jbc.m114.590554

Cited by 88 publications

(64 citation statements)

References 69 publications

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“…Histological examination showed less mononuclear cell infiltration, decreased crypt distortion, and intraparenchymal edema in colonic sections from UCB-treated compared with untreated mice ( Figure 1C Figure 1E), suggesting that UCB favors the acquisition of immunoregulatory features by pathogenic Th17 cells. The mRNA levels of heme oxygenase-1 (HO-1; Hmox1), the enzyme responsible for catalyzing the conversion of heme into biliverdin -the UCB precursor -were higher in spleen and MLN-derived mononuclear cells of mice subjected to DSS colitis when compared with DSS-untreated controls ( Figure 1F), as reported previously and in keeping with the induction of HO-1 by stress (29)(30)(31).…”

Section: Resultssupporting

confidence: 69%

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

et al. 2017

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Section: Resultssupporting

confidence: 69%

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

et al. 2017

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“…20,21 In previous studies, HO-1 was found to enhance the function of CD4 + CD25 + regulatory T cells. 13,22 Recent studies have shown that the expression of HO-1 is significantly up-regulated in T helper type 2…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5] A large number of studies have shown that HO-1 played extensive protective roles in inflammatory diseases such as asthma, 4,[6][7][8][9] inflammatory bowel disease [10][11][12][13] and uveitis. 14,15 In addition, HO-1 exerts its effects on multiple immune cells, such as promoting maturation, differentiation and function of dendritic cells, 16,17 inhibiting the antigen-presenting function of dendritic cells, 18 inducing tolerance of dendritic cells 19 and suppressing degranulation of mast cells.…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase‐1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2‐mediated allergic airway inflammation

Zhong¹,

et al. 2016

Immunology

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SummaryThe anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigeninduced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma.

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“…16,27 Moreover, the enhancement of circulating IL-10 in UC usually correlates with the changes of systemic immune responses, such as the alteration of cell subpopulations in spleens and lymph nodes or the modulation of other inflammatory factors. 28,29 Therefore, our results added to these conclusions by providing multiple evidences that exogenous IL-10 also has effect on the systemic immune responses during the treatment of UC in mice.…”

Section: Discussionmentioning

confidence: 75%

“…28,30,31 Th17 cells are a new subtype of CD4 þ T helper cells distinct from the traditional subtypes of Thl and Th2 cells. The differentiation Th17 cells is under the control of retinoic acid-related orphan receptor, which regulates the expression of IL-17 A and IL-17 F. 28,32 Consequently, CD4 þ T helper cells differentiate into Th17 cells under the influence of IL-6 and TGF-b. 33 It had been proven that Th17 cells are involved in the pathogenesis of multiple and autoimmune diseases mainly through secreting inflammatory effectors such as IL-17 A, IL-17 F, and IL-22.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 gene-carrying bifidobacteria ameliorate murine ulcerative colitis by regulating regulatory T cell/T helper 17 cell pathway

Zhang

Wei

Yao

et al. 2015

Exp Biol Med (Maywood)

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease suggested to be closely related to the imbalance of regulatory T cell/T helper 17 cell (Treg/Th17) signaling. Previously, we constructed an interleukin-10 (IL-10) expression vector, BL-hIL-10, and proved that it ameliorates dextran sulfate sodium-induced intestinal inflammation in mice. In this study, we further explored the mechanisms underlying BL-hIL-10 treatment from the Treg/Th17 imbalance perspective. Our results showed that the oral administration of BL-hIL-10 reduced the UC inflammation in mice significantly, which was assessed by disease activity index, spleen index, and pathological changes in colon tissue. Moreover, the mice after BL-hIL-10 treatment had increased proportion of Treg cells while Th17 cells decreased greatly, leading to the reconstruction of Treg/Th17 balance. Furthermore, the Th17 cell-secreted factors, such as IL-6, IL-17, and IL-23, were reduced, but the Treg-related factors, IL-10 and Transforming growth factor-b1 (TGF-b1), were elevated accordingly. Finally, Western blot confirmed the inhibition of nuclear hypoxia-inducible factor-1a (HIF-1a) and cytoplasmic mechanistic target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) in intestinal tissues. In conclusion, oral administration of BL-hIL-10 can alleviate the inflammation responses of UC in murine model through the restoration of Treg/Th17 imbalance, which might be at least partially due to the inhibition of hypoxiamTOR-HIF-1a-Th17 axis as well as IL-6-STAT3-HIF-1a-Th17 pathway.

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Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis by Regulating Th17/Treg Cell Balance

Cited by 88 publications

References 69 publications

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

Heme oxygenase‐1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2‐mediated allergic airway inflammation

Interleukin-10 gene-carrying bifidobacteria ameliorate murine ulcerative colitis by regulating regulatory T cell/T helper 17 cell pathway

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