Fgf21 regulates T-cell development in the neonatal and juvenile thymus

Abstract

We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. In line with this expression profile, Fgf21 was recently reported to protect against ageing-related thymic senescence by improving the function of thymic epithelial cells (TECs). However, the function of Fgf21 in the juvenile thymus remained to be elucidated. We investigated the physiological roles of Fgf21 in the juvenile thymus and found that young Fgf21 knockout mice, but not β-Klotho knockout mice nor adult Fgf21 knockout mice, showed a significant reduction in the percentage of single-positive CD4+ and CD8+ thymocytes without obvious alteration in TECs. Furthermore, treatment with recombinant FGF21 protein rescued the impairment in fetal thymus organ culture (FTOC) of Fgf21 knockout mice. Annexin V staining revealed FGF21 protein enhanced apoptosis of immature thymocytes undergoing selection process in FTOC, suggesting that FGF21 may facilitate the selection of developing T cells. Endocrine Fgf21 from the liver induced by metabolic stimulation did not affect juvenile thymocyte development. Our data suggest that Fgf21 acts as one of intrathymic cytokines in the neonatal and juvenile thymus, involving thymocyte development in a β-Klotho-independent manner.

Modulation of the Systemic Immune Response in Suckling Rats by Breast Milk TGF-β2, EGF and FGF21 Supplementation

“…Our results from plasma IgG, IgM and IgA concentrations in the reference group at days 14 and 21 showed that only IgA increased at the end of the suckling period, in agreement with the findings from other studies [ 45 ]. It is known that newborn rodents during the first week of life produce antibodies depending on Th2 responses, in contrast to adult rats, which show a Th1 response [ 49 , 50 , 51 ].…”

“…Previous studies also described a decrease in T cell percentage after EGF supplementation to preterm rats over 17 days [ 62 ]. Regarding FGF21, other studies did not provide comparative information; only a study contradictory to ours was found, which showed that 1- and 4-week-old FGF21-knockout mice exhibited lower percentages of CD4 + and CD8 + splenic cells, with a thymus-independent action also suggested [ 45 ]. These and other results counteracting the age-related evolutionary pattern also suggested an intriguing hypothesis, reflecting the importance of these factors maintaining immaturity rather than inducing it, which could be of importance during this particular period.…”

“…In accordance with the present results, previous studies demonstrated that oral administration of EGF (40 mg/kg/day) did not affect liver weight in rabbits [ 44 ]. In another study, the thymus and spleen of 4-week-old wild-type and FGF21-knockout mice showed similar weights [ 45 ]. However, a strong relationship between breast-fed infants and thymus size was reported in the literature, suggesting the role of breast milk components at this level [ 46 , 47 ].…”

A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

“…Physiologically, FGF-21 is reported to be expressed from tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas [9]. Secreted FGF-21 could regulate whole-body metabolism via its impact on the function of several tissues including brain and adipose tissues in an endocrine manner [10]. In white adipocytes, FGF-21 stimulates glucose uptake in an insulin-independent manner, modulates lipolysis and enhances mitochondrial oxidative capacity, and potentiates PPARγ activity [11].…”