Synthesis of Functional Tertiary Lymphoid Organs

  • Yuka Kobayashi
  • Koichi Kato
  • Makoto Nakamura
  • Takeshi Watanabe


The regeneration of functional immune organ will be one of major focus in future immunology research. It will be an useful tool which induces efficient immune responses in the body on demand and offers effective ways to restore the immune status and treat uncontrollable obstinate diseases such as cancer, autoimmune diseases, severe infection and immuno-insufficiency/deficiency caused by tissue damages, abnormality, primary defect and aging. Artificially synthesized lymphoid organs may also provide us with a highly informative method not only for clinical aim but also basic study on the development and functions of immunological tissues and organs. We first reported successful generation of artificially-constructed lymph node-like tertiary lymphoid tissues at ectopic sites in mouse by applying certain stromal cell lines (Suematsu S, Watanabe T. Nat Biotechnol 22(12):1539–1545, 2004; Okamoto N et al. J Clin Invest 117(4):997–1007, 2007; Kobayashi Y, Watanabe T. Trends Immunol 31(11):422–428, 2010). They showed a remarkable ability to induce immune responses upon antigen stimulation, especially when transplanted into naïve or immune-compromised hosts. In this review, we discuss about the rationale and method for the synthesis of functional tertiary lymph node-like lymphoid tissues in mouse. Especially, we discuss here on the method with applying only soluble factors but without using any stromal cell, that enables proper accumulation and functional organization of immune cells in grafts.


Stromal Cell Lymphoid Tissue Mesenchymal Stromal Cell Collagen Sponge Follicular Dendritic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations


secondary lymphoid organs


tertiary lymphoid organs


lymph node


Payer’s patches


dendritic cells


follicular dendritic cells


fibroblastic reticular cells


high endothelial venules


rat insulin promotor expressing Lta (lymphotoxin-α) gene


lymphoid tissue inducer


lymphoid tissue organizer


lymphotoxin receptor-beta


retinoic acid


vessel endothelial growth factor


autoimmune regulator


myeloid-derived suppressor cells

Treg cells

regulatory T cells


heparan sulfate proteoglycans


heparan sulfate


tissue-engineered spleen


germinal center


artificial antigen-presenting cells


artificial lymph nodes


induced pluripotent stem cells



This work was supported by the Grant-in-Aid for Scientific Research on Priority Areas from MEXT, Japan (Grant No. 24111009)


Authors report no conflicts of interest.


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Copyright information

© Springer Japan 2016

Authors and Affiliations

  • Yuka Kobayashi
    • 1
  • Koichi Kato
    • 2
  • Makoto Nakamura
    • 3
  • Takeshi Watanabe
    • 1
  1. 1.The Tazuke-Kofukai Medical Research Institute/Kitano HospitalKita-kuJapan
  2. 2.Department of Biomaterials Science, Graduate School of Biomedical ScienceUniversity of HiroshimaMinami-kuJapan
  3. 3.Faculty of Life Science and EngineeringUniversity of ToyamaToyamaJapan

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