Skip to main content

Advertisement

SpringerLink
Log in

Characterization of mouse mediastinal fat-associated lymphoid clusters

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs “mediastinal fat-associated lymphoid clusters”. These clusters can be considered as niches for Th cell production.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Almeida AR, Rocha B, Freitas AA, Tanchot C (2005) Homeostasis of T cell numbers: from thymus production to peripheral compartmentalization and the indexation of regulatory T cells. Semin Immunol 17:239–249

    Article  CAS  PubMed  Google Scholar 

  • Bettelli E, Oukka M, Kuchroo VK (2007) TH-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350

    Article  CAS  PubMed  Google Scholar 

  • Butler NS, Monick MM, Yarovinsky TO, Powers LS, Hunninghake GW (2002) Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice. J Immunol 169:3700–3709

    Article  CAS  PubMed  Google Scholar 

  • Charles DM, Kristi K, Jennifer MA, Michelle J (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166–6173

    Article  Google Scholar 

  • Chiossone L, Chaix J, Fuseri N, Roth C, Vivier E, Walzer T (2009) Maturation of mouse NK cells is a 4-stage developmental program. Blood 113:5488–5496

    Article  CAS  PubMed  Google Scholar 

  • Cranshaw ML, Leak LV (1990) Milky spots of the omentum: a source of peritoneal cells in the normal and stimulated animal. Arch Histol Cytol 53:165–177

    Article  PubMed  Google Scholar 

  • Elewa YH, Bareedy MH, Abuel-Atta AA, Ichii O, Otsuka S, Kanazawa T, Lee SH, Hashimoto Y, Kon Y (2010a) Cytoarchitectural differences of myoepithelial cells among goat major salivary glands. Vet Res Commun 34:557–567

    Article  PubMed  Google Scholar 

  • Elewa YH, Bareedy MH, Abuel-Atta AA, Ichii O, Otsuka S, Kanazawa T, Lee SH, Hashimoto Y, Kon Y (2010b) Structural characteristics of goat (Capra hircus) parotid salivary glands. Jpn J Vet Res 58:121–135

    PubMed  Google Scholar 

  • Fink JN (1992) Hypersensitivity pneumonitis. Clin Chest Med 13:303–309

    CAS  PubMed  Google Scholar 

  • Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T-helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170:2081–2095

    Article  CAS  PubMed  Google Scholar 

  • Fries PN, Popowych YI, Guan LL, Griebel PJ (2011) Age-related changes in the distribution and frequency of myeloid and T cell populations in the small intestine of calves. Cell Immunol 271:428–437

    Article  CAS  PubMed  Google Scholar 

  • Fulton RB, Meyerholz DK, Varga SM (2010) Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J Immunol 185:2382–2392

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gudmundsson G, Monick MM, Gary W (1998) IL-12 modulates expression of hypersensitivity pneumonitis. J Immunol 161:991–999

    CAS  PubMed  Google Scholar 

  • Handgretinger R, Kuçi S (2013) CD133-positive hematopoietic stem cells: from biology to medicine. Adv Exp Med Biol 777:99–111

    Article  CAS  PubMed  Google Scholar 

  • Hoenerhoff MJ, Starost MF, Ward JM (2006) Eosinophilic crystalline pneumonia as a major cause of death in 129S4/SvJae mice. Vet Pathol 43:682–688

    Article  CAS  PubMed  Google Scholar 

  • Ichii O, Konno A, Sasaki N, Endoh D, Hashimoto Y, Kon Y (2008) Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ. Histol Histopathol 23:411–422

    CAS  PubMed  Google Scholar 

  • Ichii O, Otsuka S, Namiki Y, Hashimoto Y, Kon Y (2011) Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis. PLoS ONE 6:e27783

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jameson SC (2002) Maintaining the norm: T-cell homeostasis. Nat Rev Immunol 2:547–556

    CAS  PubMed  Google Scholar 

  • Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    Article  CAS  PubMed  Google Scholar 

  • Koyasu S, Moro K (2011a) Type 2 innate immune responses and the natural helper cell. Immunology 132:475–481

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Koyasu S, Moro K (2011b) Innate Th2-type immune responses and the natural helper cell, a newly identified lymphocyte population. Curr Opin Allergy Clin Immunol 11:109–114

    Article  CAS  PubMed  Google Scholar 

  • Koyasu S, Tanabe M, Takeuchi T, Moro K (2010) Natural helper cells: a new player in the innate immune response against helminth infection. Adv Immunol 108:21–44

    Article  CAS  PubMed  Google Scholar 

  • Kraal G, Mebius RE (1997) High endothelial venules: lymphocyte traffic control and controlled traffic. Adv Immunol 65:347–395

    Article  CAS  PubMed  Google Scholar 

  • Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood J 106:1901–1910

    Article  CAS  Google Scholar 

  • Linda DH, Sharon MC, Byungsuk K, Ronald B (2000) Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive. Invest Ophthalmol Vis Sci 41:805–810

    Google Scholar 

  • Liu W, Putnam AL, Xu-yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, St. Groth BF, Clayberger C, Soper DM, Ziegler SF, Bluestone JA (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • MacLaren R, Cui W, Cianflone K (2008) Adipokines and the immune system: an adipocentric view. Adv Exp Med Biol 632:1–21

    Article  CAS  PubMed  Google Scholar 

  • Mannering SI, Zhong J, Cheers C (2002) T-cell activation, proliferation and apoptosis in primary Listeria monocytogenes infection. Immunology 106:87–95

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mazzucchelli R, Durum SK (2007) Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol 7:144–154

    Article  CAS  PubMed  Google Scholar 

  • Miyasaka M, Tanaka T (2004) Lymphocyte trafficking across high endothelial venules: dogmas and enigmas. Nat Rev Immunol 4:360–370

    Article  CAS  PubMed  Google Scholar 

  • Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S (2010) Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature 463:540–544

    Article  CAS  PubMed  Google Scholar 

  • Murray AB, Luz A (1990) Acidophilic macrophage pneumonia in laboratory mice. Vet Pathol 27:274–281

    CAS  PubMed  Google Scholar 

  • Nair PN, Zimmerli I, Schroeder HE (1987) Minor salivary gland duct-associated lymphoid tissue (DALT) in monkeys changes with age. J Dent Res 66:407–411

    Article  CAS  PubMed  Google Scholar 

  • Nishikawa S, Honda K, Vieira P, Yoshida H (2003) Organogenesis of peripheral lymphoid organs. Immunol Rev 195:72–80

    Article  CAS  PubMed  Google Scholar 

  • Poulin J, Sylvestre M, Champagne P, Dion M, Kettaf N, Dumont A, Lainesse M, Fontaine P, Roy D, Perreault C, Sékaly R, Cheynier R (2003) Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease. Blood 102:4600–4607

    Article  CAS  PubMed  Google Scholar 

  • Shan Y, Liu J, Jiang YJ, Shang H, Jiang D, Cao YM (2012) Age-related susceptibility and resistance to nonlethal Plasmodium yoelii infection in C57BL/6 mice. Folia Parasitol (Praha) 59:153–161

    Article  CAS  Google Scholar 

  • Sharma OP, Fujimura N (1995) Hypersensitivity pneumonitis: a noninfectious granulomatosis. Semin Respir Infect 10:96–106

    CAS  PubMed  Google Scholar 

  • Shimizu S, Sugiyama N, Masutani K, Sadanaga A, Miyazaki Y, Inoue Y, Akahoshi M, Katafuchi R, Hirakata H, Harada M, Hamano S, Nakashima H, Yoshida H (2005) Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). J Immunol 175:7185–7192

    Article  CAS  PubMed  Google Scholar 

  • Surh CD, Sprent J (2008) Homeostasis of naive and memory T cells. Immunity 29:848–862

    Article  CAS  PubMed  Google Scholar 

  • Takayama T, Kamadax N, Chinen H et al (2010) Imbalance of NKp44(+) NKp46(−) and NKp44(−) NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn’s disease. Gastroenterology 139:882–892

    Article  CAS  PubMed  Google Scholar 

  • Takemura S, Braun A, Crowson C, Kurtin PJ, Cofield RH, O’Fallon WM, Goronzy JJ, Weyand CM (2001) Lymphoid neogenesis in rheumatoid synovitis. J Immunol 167:1072–1080

    Article  CAS  PubMed  Google Scholar 

  • Taupin P (2007) BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation. Brain Res Rev 53:198–214

    Article  CAS  PubMed  Google Scholar 

  • Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt B, Veldhoen M (2011) T helper cell differentiation more than just cytokines. Adv Immunol 109:159–196

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Partnership and Ownership Initiative (ParOwn), which was funded by the Egyptian Ministry of Higher Education and the State for Scientific Research. This work was also supported by a Grant-in-Aid for Scientific Research B (no. 24380156) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Author information

Authors and Affiliations

  1. Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt

    Yaser Hosny Ali Elewa

  2. Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan

    Yaser Hosny Ali Elewa, Osamu Ichii, Saori Otsuka & Yasuhiro Kon

  3. Office for International Accreditation of Veterinary Education, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, 080-8555, Japan

    Yoshiharu Hashimoto

Authors
  1. Yaser Hosny Ali Elewa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osamu Ichii
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saori Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshiharu Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuhiro Kon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiro Kon.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1

c-Kit- and CD127-positive cells in mediastinal fat-associated lymphoid clusters (mediastinal FALCs) in C57BL/6 mice at 12 months. a, b Light micrographs of immunohistochemistry for c-Kit and CD127, respectively. Although some c-Kit-positive cells are visible in the mediastinal FALCs (arrows in a), CD127-positive cells are numerous (b). (PPT 2180 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elewa, Y.H.A., Ichii, O., Otsuka, S. et al. Characterization of mouse mediastinal fat-associated lymphoid clusters. Cell Tissue Res 357, 731–741 (2014). https://doi.org/10.1007/s00441-014-1889-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-014-1889-6

Keywords

Search

Navigation