The Function of Lyn-Deficient Regulatory Dendritic Cells in vitro
Date Issued
2015
Date
2015
Author(s)
Jian, Han-Shu
Abstract
Lyn, a Src family tyrosine kinase, is expressed in all leukocytes except T cells. Lyn has unique regulatory properties, because it not only triggers activation signals but also regulates inhibitory signals for tolerance. Lyn-deficient mice spontaneously develop an autoimmune disease that resembles human systemic lupus erythematosus (SLE), suggesting that Lyn plays a more important role in mediating inhibitory function. It has recently been reported that lyn-/- dendritic cells (DCs) enhance the capacity to induce immune responses. Actually, DCs have distinct subsets for regulating different immune responses. A special intestinal subset of DCs with characteristic of CD103 expression (CD103+ DCs) was reported involving in oral tolerance. Mouse CD103+ DCs isolated from intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) show a high level of retinoic acid (RA) production. RA, a metabolite of vitamin A, can be induced by retinal aldehyde dehydrogenase family 1, subfamily A2 (RALDH1a2), an enzyme for RA synthesis in DCs. RA plays a critical role in maintaining intestinal immune homeostasis. Thus, intestinal CD103+ DCs can induce gut-homing receptors α4β7 and CCR9 on T cells and drive the differentiation of transforming growth factor (TGF)-β-mediated Foxp3+ regulatory T (Treg) cells. Up to date, the role of Lyn tyrosine kinase in reg-DCs has not been studied. Hence, my thesis is to study whether Lyn tyrosine kinase affect the function of reg-DCs. First, I established bone marrow-derived reg-DCs in vitro culture and compared the function between wild type (WT) and lyn-/- reg-DCs. Second, I examined the phenotype of reg-DCs in lyn-/- mice. The results showed that Lyn deficiency led the lower RALDH1a2 activity in reg-DCs in vitro. Also, lyn-/- reg-DCs impaired the function of inducing CD4+ Foxp3+ Treg cells in vitro. In addition, lyn-/- reg-DCs impaired maturation after innate immune stimulation. Consistent with in vitro data, reg-DCs in lyn-/- MLN showed lower RALDH1a2 activity. These results suggested that lyn-/- mice may have weak reg-DC function compared to WT mice and lead to autoimmune disease. Also, these results suggested that Lyn may positively regulate the function of reg-DCs. However, the mechanism of how Lyn participates in reg-DCs function needs to be further explored.
Subjects
Lyn
regulatory dendritic cell
CD103+ DC
RALDH1a2
regulatory T cell
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-104-R01449004-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):4cb14569f3c6f30105e144fbcbc460e5