Nerve growth factor stimulates proliferation, adhesion and thymopoietic cytokine expression in mouse thymic epithelial cells in vitro Hee-Woo Lee a,1,2 , Yong-Jin Na b,c,1 , Pil-Ku Jung a , Mi-Na Kim a , Sung-Min Kim a,2 , Joo-Seop Chung d , Bong-Seon Kim a , Jae-Bong Kim a , Jeon-Ok Moon e , Sik Yoon a,c,f,g, ⁎ a Department of Anatomy, Pusan National University School of Medicine, Seo-Gu, Busan, South Korea b Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Seo-Gu, Busan, South Korea c Medical Research Institute, Pusan National University School of Medicine, Seo-Gu, Busan, South Korea d Department of Hematology, Pusan National University School of Medicine, Seo-Gu, Busan, South Korea e College of Pharmacy, Pusan National University, Keumjeong-Gu, Busan, South Korea f Medical Research Center for Ischemic Tissue Regeneration, Seo-Gu, Busan, South Korea g Medical Research Institute, Pusan National University Medical Science Education Center (BK21 program), Pusan National University School of Medicine, Seo-Gu, Busan, South Korea Received 26 July 2007; received in revised form 24 November 2007; accepted 2 January 2008 Available online 16 January 2008 Abstract Thymic epithelial cells, which constitute a major component of the thymic microenvironment, provide a crucial signal for intrathymic T cell development and selection. Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. NGF is increasingly recognized as a potent immunomodulator, promoting “cross-talk” between various types of immune system cells. The present study clearly shows that NGF stimulates mouse thymic epithelial cell activities in vitro including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7, GM-CSF, SDF-1, TARC and TECK. Thus, our data are of considerable clinical importance showing that trophic NGF activity could be used to enhance the thymus regeneration and develop methods to improve host immunity when the immune function is depressed due to thymic involution. © 2008 Elsevier B.V. All rights reserved. Keyword: Nerve growth factor (NGF); Thymic epithelial cells; Thymocytes; Cell adhesion molecule; Thymopoietic cytokine 1. Introduction The thymus, the central lymphoid organ, is a complex epi- thelial organ in which thymocyte development is dependent upon the sequential contribution of morphologically and phenotypi- cally distinct stromal cell compartments that comprise the thymic microenvironment [1–3]. The unique combination of cellular interactions, cytokines, and chemokines within this microenvir- onment induces thymocyte precursors to undergo a differentiation program that leads to the generation of functional T cells. Thymic epithelial cells, which constitute a major component of the stromal cells of the thymus, provide a crucial signal for intrathymic T cell development and selection, and are mainly divided into four groups (subcapsular/paraseptal/perivascular epithelium; cortical epithelium; medullary epithelium; Hassall's corpuscles) accord- ing to their epithelial staining pattern in the thymus [4–6]. With advancing age, the thymus undergoes a physiological process of involution, whereby the production of T cells declines and the parenchyma becomes largely replaced by adipose tissue. Moreover, this gradual process of physiological or age involution can be acutely accelerated by the so-called acute or accidental involution of thymus. This may occur in response to various stimuli including disease, severe stress, ionizing radiation, adrenal Available online at www.sciencedirect.com Regulatory Peptides 147 (2008) 72 – 81 www.elsevier.com/locate/regpep ⁎ Corresponding author. Department of Anatomy, Pusan National University School of Medicine, Seo-Gu, Busan, South Korea. Tel.: +82 51 240 7720; fax: +82 51 248 1023. E-mail address: sikyoon@pusan.ac.kr (S. Yoon). 1 Denotes co-first authors. 2 Current address: Department of Microbiology (BK21 project), School of Medicine, Kyungpook National University, Daegu, 700-422, South Korea. 0167-0115/$ - see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.regpep.2008.01.004