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Synthesis of Functional Tertiary Lymphoid Organs

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Synthetic Immunology

Abstract

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.

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Abbreviations

SLO:

secondary lymphoid organs

TLO:

tertiary lymphoid organs

LN:

lymph node

PP:

Payer’s patches

DC:

dendritic cells

FDC:

follicular dendritic cells

FRC:

fibroblastic reticular cells

HEV:

high endothelial venules

RIP- LTα:

rat insulin promotor expressing Lta (lymphotoxin-α) gene

LTi:

lymphoid tissue inducer

LTo:

lymphoid tissue organizer

LTRβ:

lymphotoxin receptor-beta

RA:

retinoic acid

VEGFc:

vessel endothelial growth factor

Aire:

autoimmune regulator

MDSCs:

myeloid-derived suppressor cells

Treg cells:

regulatory T cells

HSPGs:

heparan sulfate proteoglycans

HS:

heparan sulfate

TES:

tissue-engineered spleen

GC:

germinal center

aAPC:

artificial antigen-presenting cells

aLN:

artificial lymph nodes

iPS:

induced pluripotent stem cells

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Acknowledgements

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

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Authors report no conflicts of interest.

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Authors and Affiliations

  1. The Tazuke-Kofukai Medical Research Institute/Kitano Hospital, Kita-ku, Osaka, 530-8480, Japan

    Yuka Kobayashi & Takeshi Watanabe

  2. Department of Biomaterials Science, Graduate School of Biomedical Science, University of Hiroshima, Minami-ku, Hiroshima, 734-8553, Japan

    Koichi Kato

  3. Faculty of Life Science and Engineering, University of Toyama, Gofuku 3190, Toyama, 930-8555, Japan

    Makoto Nakamura

Authors
  1. Yuka Kobayashi
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  2. Koichi Kato
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  3. Makoto Nakamura
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  4. Takeshi Watanabe
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Correspondence to Takeshi Watanabe .

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Editors and Affiliations

  1. Kitano Hospital, Kita-ku, Osaka, Japan

    Takeshi Watanabe

  2. Division of Experimental Immunology, University of Tokushima, Tokushima, Japan

    Yousuke Takahama

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Kobayashi, Y., Kato, K., Nakamura, M., Watanabe, T. (2016). Synthesis of Functional Tertiary Lymphoid Organs. In: Watanabe, T., Takahama, Y. (eds) Synthetic Immunology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56027-2_7

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