Fatty acid-binding protein 4 (FABP4) and FABP5 modulate cytokine production in the mouse thymic epithelial cells

Abstract

Thymic stromal cells, including cortical thymic epithelial cells (cTEC) produce many humoral factors, such as cytokines and eicosanoids to modulate thymocyte homeostasis, thereby regulating the peripheral immune responses. In this study, we identified fatty acid-binding protein (FABP4), an intracellular fatty acid chaperone, in the mouse thymus, and examined its role in the control of cytokine production in comparison with FABP5. By immunofluorescent staining, FABP4+ cells enclosing the thymocytes were scattered throughout the thymic cortex with a spatial difference from the FABP5+ cell that were distributed widely throughout the cTEC. The FABP4+ cells were immunopositive for MHC class II, NLDC145 and cytokeratin 8, and were identified as part of cTEC. The FABP4+ cells were identified as thymic nurse cells (TNC), a subpopulation of cTEC, by their active phagocytosis of apoptotic thymocytes. Furthermore, FABP4 expression was confirmed in the isolated TNC at the gene and protein levels. To explore the function of FABP in TNC, TSt-4/DLL1 cells stably expressing either FABP4 or FABP5 were established and the gene expressions of various cytokines were examined. The gene expression of interleukin (IL)-7 and IL-18 was increased both in FABP4 and FABP5 over-expressing cells compared with controls, and moreover, the increase in their expressions by adding of stearic acids was significantly enhanced in the FABP4 over-expressing cells. These data suggest that both FABPs are involved in the maintenance of T lymphocyte homeostasis through the modulation of cytokine production, which is possibly regulated by cellular fatty acid-mediated signaling in TEC, including TNC.

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Acknowledgments

We cordially thank Dr. Willem V. Ewijk (Leiden University Medical Center, Leiden, The Netherlands) and Dr. Takashi Amagai for providing ER-TR4 antibody. We grateful thank to Dr. Hiroshi Kawamoto (RIKEN Research Center for Allergy and Immunology, Yokohama, Japan) for his useful comments and providing TSt-4 and TSt-4/DLL-1 cells, and Dr. Tsunetoshi Itoh (Tohoku University Graduate School of Medicine, Sendai, Japan) for providing IT-79MTNC cells. This work was supported by Grant-in-Aid for Young Scientists (B) to Y.A. (No. 19790152) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, from the New Frontier Project Research Fund of Yamaguchi University Graduate School of Medicine to Y.A. and from the Yamaguchi University Research Project on STRESS.

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Correspondence to Yasuhiro Adachi or Yuji Owada.

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Y. Adachi and S. Hiramatsu contributed equally to this work.

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Adachi, Y., Hiramatsu, S., Tokuda, N. et al. Fatty acid-binding protein 4 (FABP4) and FABP5 modulate cytokine production in the mouse thymic epithelial cells. Histochem Cell Biol 138, 397–406 (2012). https://doi.org/10.1007/s00418-012-0963-y

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Keywords

  • Fatty acid-binding protein
  • Thymus
  • Thymic epithelial cells
  • Thymic nurse cells
  • IL-7
  • IL-18