Histamine enhances TGF‐β1‐mediated suppression of Th2 responses

Kunzmann, Steffen; Mantel, Pierre‐Yves; Wohlfahrt, Jan G.; Akdiş, Mübeccel; Blaser, Kurt; Schmidt‐Weber, Carsten B.

doi:10.1096/fj.02-1008com

Cited by 86 publications

(51 citation statements)

References 38 publications

(54 reference statements)

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“…Increased IL-10 production in both DCs and T cells may account for an important regulatory mechanism in the control of inflammatory functions through histamine. In accordance with this phenomenon, it has recently been demonstrated that histamine supports the suppressive effect of TGF-␤ on T cells via HR2 [189]. Th2 cells are more affected by histamineenhanced TGF-␤ suppression, which is particularly important for the regulation of allergen-specific T cells in allergic immune responses.…”

Section: P R O O Fmentioning

confidence: 57%

“…In addition, histamine induces IL-10 production by Th2 cells [188]. Furthermore, histamine enhances the suppressive activity of TGF-␤ on T cells [189]. All three of these effects are mediated via HR2, which is relatively highly expressed on Th2 cells and suppresses IL-4 and IL-13 production and T-cell proliferation [49].…”

Section: Clinical Evidence For T-regulatory Function Of Histamine Recmentioning

confidence: 99%

See 1 more Smart Citation

T-Cell Regulatory Mechanisms in Specific Immunotherapy

Jutel

Akdiş²

2008

Chemical Immunology and Allergy

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Section: P R O O Fmentioning

confidence: 57%

Section: Clinical Evidence For T-regulatory Function Of Histamine Recmentioning

confidence: 99%

T-Cell Regulatory Mechanisms in Specific Immunotherapy

Jutel

Akdiş²

2008

Chemical Immunology and Allergy

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“…Increased IL-10 production in both DC and T cells may account for an important regulatory mechanism in the control of inflammatory functions through histamine. In accordance with this phenomenon, it has recently been demonstrated that histamine supports the suppressive effect of TGF-b on T cells via HR2 (195). The Th2 cells are more affected by histamine-enhanced TGF-b suppression, which is particularly important for the regulation of allergenspecific T cells in allergic immune responses.…”

Section: Camp Stimulating G-protein Coupled Receptors In Peripheral Tmentioning

confidence: 57%

“…In addition, histamine induces IL-10 production by Th2 cells (194). Furthermore, histamine enhances the suppressive activity of TGF-b on T cells (195). All three of these effects are mediated via HR2, which is relatively highly expressed on Th2 cells and suppresses IL-4 and IL-13 production and T-cell proliferation (40).…”

Section: Clinical Evidence For T Regulatory Function Of Histamine Recmentioning

confidence: 99%

Genes of tolerance

Akdiş¹,

Blaser²,

Akdiş³

2004

Allergy

Self Cite

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Activation‐induced cell death, anergy and/or immune response modulation by T‐regulatory cells (TReg) are essential mechanisms of peripheral T‐cell tolerance. There is growing evidence that anergy, tolerance and active suppression are not entirely distinct, but rather, represent linked mechanisms possibly involving the same cells and multiple suppressor mechanisms. Skewing of allergen‐specific effector T cells to TReg cells appears as a crucial event in the control of healthy immune response to allergens and successful allergen‐specific immunotherapy. The TReg cell response is characterized by abolished allergen‐induced specific T‐cell proliferation and suppressed T helper 1 (Th1)‐ and Th2‐type cytokine secretion. In addition, mediators of allergic inflammation that trigger cAMP‐associated G‐protein coupled receptors, such as histamine receptor 2 may contribute to peripheral tolerance mechanisms. The increased levels of interleukin‐10 (IL‐10) and transforming growth factor‐β (TGF‐β) that are produced by TReg cells potently suppress immunoglobulin E (IgE) production, while simultaneously increasing production of noninflammatory isotypes IgG4 and IgA, respectively. In addition, TReg cells directly or indirectly suppress effector cells of allergic inflammation such as mast cells, basophils and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms. It is associated with regulation of antibody isotypes and effector cells to the direction of a healthy immune response and opens a window for novel therapies of allergic diseases.

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“…In addition, histamine induces IL-10 production by Th2 cells [55]. Furthermore, histamine enhances the suppressive activity of TGF-β on T cells [58]. All of these three effects are mediated via HR2, which is relatively highly expressed on Th2 cells and suppresses IL-4 and IL-13 production and T cell proliferation [53].…”

Section: Regulation Of Immune Responsementioning

confidence: 99%

Histamine in Allergic Inflammation and Immune Modulation

Jutel¹,

Blaser²,

Akdiş³

2005

Int Arch Allergy Immunol

117

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Histamine, originally considered as a mediator of acute inflammatory and immediate hypersensitivity responses has also been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. On the other hand, various cytokines control histamine synthesis, release and expression of histamine receptors (HRs). The cells involved in the regulation of immune response and hematopoiesis express HRs and also secrete histamine, which can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization and effector functions leading to chronic inflammation. Histamine, acting through its receptor type 2, positively interferes with the peripheral antigen tolerance induced by T regulatory cells in several pathways. Histamine also regulates antigen-specific Th1 and Th2 cells, as well as related antibody isotype responses. The diverse effects of histamine on immune regulation are due to differential expression and regulation of four HRs and their distinct intracellular signals. In addition, differences in affinities of these receptors are highly decisive on the biological effects of histamine and agents that target HRs. This article highlights the findings leading to a change of perspective in histamine immunobiology.

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Histamine enhances TGF‐β1‐mediated suppression of Th2 responses

Cited by 86 publications

References 38 publications

T-Cell Regulatory Mechanisms in Specific Immunotherapy

T-Cell Regulatory Mechanisms in Specific Immunotherapy

Genes of tolerance

Histamine in Allergic Inflammation and Immune Modulation

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