Effects of High-Dose Dexamethasone on Regulating Interleukin-22 Production and Correcting Th1 and Th22 Polarization in Immune Thrombocytopenia

Cao, Jiang; Chen, Chong; Li, Li; Zeng, Lingyu; Li, Zhenyu; Zhang, Yan; Chen, Wei; Cheng, Hai; Sang, Wei; Xu, Kailin

doi:10.1007/s10875-012-9649-4

Cited by 47 publications

(32 citation statements)

References 29 publications

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“…For example, the chemokine CX3CL1/fractalkine known for its ability to promote the survival of CD16 ϩ monocytes 37 was elevated, albeit not statistically significant, in blood and bone marrow of ITP patients. 38 The expansion of CD16 ϩ monocytes (our study) and/or their potential heightened activation state 34 in ITP may be responsible for the previously described skewed Th1 responses, [12][13][14]26 which was also confirmed in this study. We did not analyze platelet antigen-specific Th1 responses, but our working hypothesis is that the increase in Th1 responses will ultimately augment antigenspecific Th1 responses through positive feedback mechanisms.…”

Section: Discussionsupporting

confidence: 83%

“…21 More recently, studies reported increased Th17 cells or IL-17 cytokine in ITP patients, [22][23][24] implicating a possible role for Th17 cells in ITP immunopathology, although 2 reports did not detect any difference. 25,26 Among the treatment options available to ITP patients, the recently licensed thrombopoietic agents, by increasing platelet production, have yielded overall durable responses in patients with persistent, chronic, and/or refractory ITP while on treatment. 27 Interestingly, improved Treg function in ITP patients was associated with increased platelet counts after the use of these agents, 28 despite apparent lack of immunomodulatory activity associated with such agents.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, improved Treg compartment was reported in ITP patients with a platelet response to rituximab, 18 and treatment with high-dose dexamethasone was shown to increase the frequency of circulating Tregs 17 as well as decrease Th1 cells. 26 In the present study, we explored the role of monocyte subsets in polarization of Th subsets in patients with ITP. Our findings are consistent with ITP CD16 ϩ monocytes promoting Th1 development, which in turn negatively regulates IL-17 and Treg induction, thus providing a potential mechanism for the formation of potentially pathogenic Th cells in this autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

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CD16+ monocytes control T-cell subset development in immune thrombocytopenia

Zhong

Bao

et al. 2012

Blood

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IntroductionClassic differentiation of naive CD4 ϩ T cells into different T helper (Th) subsets, including Th1, Th2, and Th17, occurs in lymphoid tissues after contact with antigen-presenting cells that produce polarizing cytokines. These Th subsets in turn orchestrate diverse immune responses also mediated by production of distinct cytokines. Because aberrant Th1 or Th17 activities have the potential to trigger chronic inflammatory and autoimmune diseases, 1,2 effector Th responses in healthy persons are under tight regulation mediated in part by CD4 ϩ regulatory T cells (Tregs) that are thymic-derived or naive T cell-inducible. 3 Understanding how Th1/Th17/Treg differentiation and expansion are controlled is likely to provide an explanation of how inflammation may be sustained in pathologic environments.More recently, human monocytes were shown to trigger and polarize Th responses 4,5 as well as to both stimulate and suppress T-cell responses during infection and in autoimmune diseases. 5,6 Monocytes, which are generally regarded as precursors of tissue macrophages and dendritic cells, 7 can be phenotypically divided based on surface expression of CD14 (lipopolysaccharide receptor) and CD16 (low affinity Fc␥ receptor III) expression into subsets, each with distinct functional activities. The major monocyte subpopulation characterized by high CD14 but no CD16 expression (CD14 hi CD16 Ϫ ), also referred to as classic monocytes, have higher phagocytic activity. 8 The minor CD16 ϩ cells produce higher TNF after stimulation and expand under infectious or inflammatory conditions. 9,10 With regards to the control of Th differentiation and reactivation, the specific role of the monocyte subsets has not been fully characterized.Immune thrombocytopenia (ITP) is an autoimmune bleeding disease resulting from decreased platelet production as well as accelerated platelet destruction mediated in part by autoantibody-based destruction mechanisms. 11 ITP patients harbor activated platelet-autoreactive T cells with increasing cytokine imbalance toward IL-2 and IFN-␥ 12-14 as well as altered Treg numbers and function. [15][16][17][18][19][20] A shift toward stimulatory monocytes with enhanced Fc␥R-mediated phagocytic capacity further supports a generalized immune dysregulation in ITP. 21 More recently, studies reported increased Th17 cells or IL-17 cytokine in ITP patients, 22-24 implicating a possible role for Th17 cells in ITP immunopathology, although 2 reports did not detect any difference. 25,26 Among the treatment options available to ITP patients, the recently licensed thrombopoietic agents, by increasing platelet production, have yielded overall durable responses in patients with persistent, chronic, and/or refractory ITP while on treatment. 27 Interestingly, improved Treg function in ITP patients was associated with increased platelet counts after the use of these agents, 28 despite apparent lack of immunomodulatory activity associated with such agents. Similarly, improved Treg compartment was reported in ITP patients w...

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD16+ monocytes control T-cell subset development in immune thrombocytopenia

Zhong

Bao

et al. 2012

Blood

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“…In addition, Th1 cells from patients with immune thrombocytopenia are sensitive to glucocorticoid inhibition [69]. Similarly, glucocorticoids decrease Th2 cytokines IL-4, IL-5, and IL-13 in vitro [70, 71] as well as Th2 cytokines in T cells from asthma patients [72].…”

Section: Distinct Sensitivity Of Th Cytokines To Glucocorticoid Sumentioning

confidence: 99%

A gradient of glucocorticoid sensitivity among helper T cell cytokines

Banuelos

2016

Cytokine & Growth Factor Reviews

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Helper T (Th) cells secret specific cytokines that promote immune responses whereas glucocorticoids limit the extent of immune responses by inhibiting cytokine secretion and other functions of Th cells. However, glucocorticoid resistance develops in subgroups of patients with Th cell-driven diseases such as asthma and Crohn’s disease. Recent evidence supports that Th1, Th2, and Th17 cells have distinct glucocorticoid sensitivity. Th1 cells are sensitive to glucocorticoid-induced apoptosis and cytokine suppression while Th2 cells are sensitive to the latter but not the former and Th17 cells are resistant to both. This gradient of glucocorticoid sensitivity of Th cells corresponds to the glucocorticoid sensitivity of the diseases they underlie. We identify the mechanisms contributing to distinct glucocorticoid sensitivity of Th cells and their cytokines in the literature, as this information is useful to improve treatment strategies for glucocorticoid resistant immunological disorders.

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“…Treatment with GCs reduces the frequency of peripheral blood IL-22 T cells and the levels of plasma IL-22 in patients with acute bacterial infection [21]. High-dose dexamethasone reduced IL-22 production in immune thrombocytopenia [22]. CYC is a well-established immunodepressant known to influence cell cycle and DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%