Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura

Zhang, Jingbo; Ma, Daoxin; Zhu, Xiaojuan; Qu, Xun; Ji, Chunyan; Hou, Ming

doi:10.3324/haematol.2009.007823

Cited by 120 publications

(105 citation statements)

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“…Similarly to the results of Zhang et al, 15 the percentage of CD4+/IL-17+ cells was significantly higher (P=0.05) in patients with cITP (1.63±1.23) than in controls (0.62±0.21) (Figure 2A and B), whereas the percentage of CD8+/IL-17+ cells did not differ (P=0.30) between patients (0.78±0.29) and controls (0.59±0.41). Notably, we also demonstrated that the percentage of neutrophils expressing IL-17A was significantly higher (P=0.001) in patients with cITP than in controls (0.98±0.32 and 0.51±0.19, respectively) (Figure 2A and B).…”

Section: Resultssupporting

confidence: 64%

“…12 However, few studies to date have evaluated the Th17 cell associated cytokines in cITP, all of them included only Chinese populations and there is little agreement between results. [13][14][15][16] Whereas Zhang et al 15 demonstrated increased intracellular levels of Th17 and Th1 cell cytokines in patients with cITP, no significant differences in the serum levels or in the expression of IL-17 by peripheral blood mononuclear cells were observed in patients with cITP in the studies of Ma et al 13 and Guo et al, 14 respectively. Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia.…”

Section: Introductionmentioning

confidence: 79%

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The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

Rocha¹,

Souza²,

Rocha³

et al. 2011

Haematologica

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Section: Resultssupporting

confidence: 64%

Section: Introductionmentioning

confidence: 79%

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

Rocha¹,

Souza²,

Rocha³

et al. 2011

Haematologica

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“…This argument is further strengthened by recent evidence that Th17 cells can provide B-cell help in murine autoantibody-induced arthritis 41 and that B-cell activity in patients with acute viral myocarditis correlated positively with IL-17, but not IFN-γ. 42 Increased levels of IL-17 and Th17 cells have also been reported in the blood of patients with autoimmune thrombocytopenia 43,44 supporting the view that the Th17 subset contributes to pathology in a variety of autoantibody-mediated diseases.…”

Section: Discussionmentioning

confidence: 86%

Production of the effector cytokine interleukin-17, rather than interferon- , is more strongly associated with autoimmune hemolytic anemia

et al. 2012

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BackgroundInterleukin-17A is the signature cytokine of the Th17 subset and drives inflammatory pathology, but its relevance to autoantibody-mediated diseases is unclear. Th1 cells secreting interferon-γ have been implicated in autoimmune hemolytic anemia, so the aim was to determine which cytokine is more closely associated with disease severity. Design and MethodsInterferon-γ and interleukin-17A were measured in the sera of patients with autoimmune hemolytic anemia and healthy donors, and in peripheral blood mononuclear cell cultures stimulated with autologous red blood cells, or a panel of peptides spanning red blood cell autoantigen. ResultsSerum interleukin-17A, but not interferon-γ, was significantly raised in patients with autoimmune hemolytic anemia (P<0.001), and correlated with the degree of anemia. Interleukin-17A was also more prominent in the responses of peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia to red blood cells, and, again unlike interferon-γ, significantly associated with more severe anemia (P<0.005). There were no interleukin-17A responses to red blood cells by peripheral blood mononuclear cells from healthy donors. Specific autoantigenic peptides were identified that elicit patients' interleukin-17A responses. ConclusionsInterleukin-17A makes a previously unrecognized contribution to the autoimmune response in autoimmune hemolytic anemia, challenging the model that the disease is driven primarily by Th1 cells. This raises the possibility that Th17, rather than Th1, cells should be the target for therapy.

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“…[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][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.…”

Section: Introductionmentioning

confidence: 99%

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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Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura

Cited by 120 publications

References 10 publications

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

Production of the effector cytokine interleukin-17, rather than interferon- , is more strongly associated with autoimmune hemolytic anemia

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

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