Atopic dermatitis and skin diseaseInduced CD4+ forkhead box protein–positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1
Section snippets
Animals
BALB/c mice were obtained from Jackson Laboratories (Bar Harbor, Me). All animal care and experiments were performed under institutional protocols approved by the University of Southern California Institutional Animal Care and Use Committee.
Cell culture
BALB/c splenic naive CD4+CD25−CD62L+CD44low cells were isolated by means of negative selection, as described previously.9, 18 CD4+CD25−CD62L+CD44low cells were stimulated with anti-CD3/CD28 beads (one bead to 5 cells [1:5]) and IL-2 (40 U/mL) with (iTreg
iTreg cells inhibit proinflammatory cytokine release by MCs activated in an IgE-independent manner
Recent studies demonstrated an interaction between murine MCs and nTreg cells.6, 7, 8 nTreg cells inhibit MC degranulation but not inflammatory cytokine secretion when activated in an IgE-dependent manner.6 However, it is unknown whether iTreg cells modulate MC function or Treg cells alter proinflammatory cytokine production by MCs that are activated in an IgE-independent manner. To address this question, BMMCs were induced from bone marrow cells after stimulating with IL-3 for 4 to 6 weeks at
Discussion
In this study we demonstrated that iTreg cells significantly inhibit TNF-α and IL-6 production by MCs activated through a non-IgE trigger in vitro, possibly by inhibiting NF-κB activation. Importantly, we also observed a similar inhibitory effect in human cells. Using an MC-driven CHS murine model, we demonstrated that systemic administration of iTreg cells attenuated established CHS coupled with a significant decrease in MC frequency and size, as well as decreased TNF-α and IL-6 production,
References (58)
- et al.
CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction
Immunity
(2008) - et al.
Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation
Blood
(2009) - et al.
Establishment of an immature mast cell line from a patient with mast cell leukemia
Leuk Res
(1988) - et al.
Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells
Biochim Biophys Acta
(2003) - et al.
Sulindac inhibits activation of the NF-kappaB pathway
J Biol Chem
(1999) - et al.
Mast cell-derived tumor necrosis factor can promote nerve fiber elongation in the skin during contact hypersensitivity in mice
Am J Pathol
(2006) - et al.
Abrogation of high-affinity IgE receptor-mediated mast cell activation at the effector phase prevents contact hypersensitivity to oxazolone
J Invest Dermatol
(2010) - et al.
Mast cell participation during the elicitation of murine allergic contact hypersensitivity
J Invest Dermatol
(1987) - et al.
TGF-beta: a master of all T cell trades
Cell
(2008) - et al.
Allergic skin diseases
J Allergy Clin Immunol
(2010)
Mast cells regulate the magnitude and the cytokine microenvironment of the contact hypersensitivity response
Am J Pathol
Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens
Immunity
Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data
Nat Rev Immunol
The master switch: the role of mast cells in autoimmunity and tolerance
Annu Rev Immunol
Immunomodulatory mast cells: negative, as well as positive, regulators of immunity
Nat Rev Immunol
Mast cells in the development of adaptive immune responses
Nat Immunol
Mast cells as modulators of T-cell responses
Immunol Rev
Mast cells down-regulate CD4+CD25+ T regulatory cell suppressor function via histamine H1 receptor interaction
J Immunol
Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors
J Immunol
CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome
J Immunol
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3
J Exp Med
Induced Foxp3+ regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases
J Mol Cell Biol
Cutting edge: Foxp3+CD4+CD25+ regulatory T cells induced by IL-2 and TGF-beta are resistant to Th17 conversion by IL-6
J Immunol
Myelin-reactive, TGF-beta-induced regulatory T cells can be programmed to develop Th1-like effector function but remain less proinflammatory than myelin-reactive Th1 effectors and can suppress pathogenic T cell clonal expansion in vivo
J Immunol
Cutting edge: all-trans retinoic Acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu
J Immunol
Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells
Arthritis Rheum
CD4+CD25+ immunoregulatory T cells may not be involved in controlling autoimmune arthritis
Arthritis Res Ther
IL-2 is essential for TGF-beta to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells
J Immunol
Isolation of purified and live Foxp3+ regulatory T cells using FACS sorting on scatter plot
J Mol Cell Biol
Cited by (58)
Demonstration and implications of IL-3 upregulation of CD25 expression on human mast cells
2022, Journal of Allergy and Clinical ImmunologyImmunogenetic perspective of inflammatory disorders
2022, Immunogenetics: a Molecular and Clinical Overview: Clinical Applications of Immunogenetics, Volume IIThe progress and prospect of regulatory T cells in autoimmune diseases
2020, Journal of AutoimmunityTraitor or warrior–Treg cells sneaking into the lesions of psoriatic arthritis
2020, Clinical ImmunologyInsight into interleukin-37: The potential therapeutic target in allergic diseases
2019, Cytokine and Growth Factor Reviews
Supported in part by grants from National Institutes of Health (AR059103 and AI084359), the ACR Within Our Reach Fund, the Arthritis Foundation, the Wright Foundation, the Guangdong Provincial Department University Industry Cooperation Project (2010B090400415), the International Collaborative Projects of Shanghai Municipal Science and Technology Commission (11410702000), the Fujian Science and Technique Foundation (2009I0008), and the Department of Veterans Affairs.
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
- ∗
These authors contributed equally to this work.