Plasticity in the differentiation of IL-22 producing cells (P6265)

Abstract

Abstract T helper type 22 (Th22) cells are a subset of CD4+ effector T cell that primarily produces interleukin 22 (IL-22), IL-13, and TNF-alpha and have an indispensable role in host defense, barrier function, tissue repair and inflammation. However, the stability and plasticity of Th22 cells have not been elucidated. In this study we developed an IL-22-tdTomato reporter mouse to examine the plasticity of Th22 cells in vitro and in vivo. Briefly, a bacterial artificial chromosome (BAC) was modified to introduce the fluorescent reporter gene into the Il-22 locus. By homologous recombination, the synthesis of the signal peptide of Il-22 in the BAC was disrupted and the tdTomato gene with poly A was inserted immediately after the ATG start site of Il-22, replacing exon 1. Mice were generated that harbor the BAC construct. We found that in vitro generated Th22 cells still maintained their differentiation program in vitro in the early stage of development and could be reprogrammed into Th17 and Th1 cell lineages, but not Th2 cells, in the later stage. To observe Th22 plasticity in vivo, we sorted IL-22 producing cells from mouse T cell transferred colitis model and injected them back to the Rag-/- mouse. It demonstrated that Th22 cells slowly lost their IL-22 expression and converted into Th17 cells in a TGF-beta dependent manner. These results, although suggesting the flexibility of Th22 cells, also indicate active maintenance of their program in vivo.