Advertisement

Mast Cells pp 461-486 | Cite as

Studying Mast Cells in Peripheral Tolerance by Using a Skin Transplantation Model

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1220)

Abstract

Mast cells (MCs) play an important role in both inflammatory and immunosuppressive responses [1]. The importance of MCs in maintaining peripheral tolerance was discovered in a FoxP3+ regulatory T-cell (Treg)-mediated skin transplant model [2]. MCs can directly mediate tolerance by releasing anti-inflammatory mediators (reviewed in ref. 3) or by interacting with other immune cells in the graft. Here we will present protocols used to study the role of MCs in peripheral tolerance with the emphasis on how MCs can regulate T-cell functionality. First we will introduce the skin transplant model followed by reconstitution of mast cell-deficient mice (B6.Cg-Kit W-sh ). This includes the preparation of MCs from the bone marrow. Finally the methods used to study the influence of MCs on T-cell responses and Treg functionality will be presented by modulating the balance between tolerance and inflammation.

Key words

Peripheral tolerance Transplantation Skin Mast cells Degranulation Inflammation Regulatory T cells 

References

  1. 1.
    Galli SJ, Grimbaldeston M, Tsai M (2008) Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol 8(6):478–486PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Lu LF et al (2006) Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 442(7106):997–1002PubMedCrossRefGoogle Scholar
  3. 3.
    de Vries VC, Noelle RJ (2010) Mast cell mediators in tolerance. Curr Opin Immunol 22(5):643–648PubMedCrossRefGoogle Scholar
  4. 4.
    de Vries VC et al (2011) Mast cells condition dendritic cells to mediate allograft tolerance. Immunity 35(4):550–561PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    de Vries VC et al (2009) Mast cell degranulation breaks peripheral tolerance. Am J Transplant 9(10):2270–2280PubMedCrossRefGoogle Scholar
  6. 6.
    de Vries VC et al (2009) The enigmatic role of mast cells in dominant tolerance. Curr Opin Organ Transplant 14(4):332–337PubMedCrossRefGoogle Scholar
  7. 7.
    Miller DM et al (2009) TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade. J Immunol 182(9):5547–5559PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Elgueta R et al (2009) Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev 229(1):152–172PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Laboratory of Allergy and Inflammation, Singapore Immunology Network (SIgN)Agency for Science, Technology and Research (A*STAR)SingaporeSingapore
  2. 2.Department of Microbiology and ImmunologyDartmouth Medical School and Norris Cotton Cancer CenterLebanonUSA
  3. 3.King’s Health Partners, Medical Research Council (MRC) Centre of TransplantationKing’s College London, Guy’s HospitalLondonUK
  4. 4.Norris Cotton Cancer CenterLebanonUSA

Personalised recommendations