Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

Acute graft-versus-host disease(a GVHD)is caused by allo-activated donor T cells infiltrating target organs.As a regulator of immune function,granulocyte colony-stimulating factor(G-CSF)has been demonstrated to relieve the a GVHD reaction.However,the role of G-CSF-primed donor Tcells in specific target organs is still unknown.In this study,we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c)and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group.This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model,especially in the lung and gut.Moreover,we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs.In addition,G-CSF treatment inhibited inducible co-stimulator(ICOS)expression and increased the expression of tolerance-related genes in recipient mice.Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD,especially for its precise regulation in GVHD target organs.

IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

Interleukin- 13 interferes with activation-induced t-ce apoptosis by repressing p53 expression

The etiology and the underlying mechanism of CD4＋ T-cell polarization are unclear. This study sought to investigate the mechanism by which interleukin （IL）-13 prevents the activation-induced apoptosis of CD4＋ T cells. Here we report that CD4＋ T cells expressed IL-13 receptor a2 in the intestine of sensitized mice. IL-13 suppressed both the activation-induced apoptosis of CD4＋ T cells and the expression of p53 and FasL. Exposure to recombinant IL-13 inhibited activation-induced cell death （AICD） along with the expression of p53, caspase 3, and tumor necrosis factor-a in CD4＋ T cells. Administration of an anti-lL-13 antibody enhanced the effect of specific immunotherapy on allergic inflammation in the mouse intestine, enforced the expression of p53 in intestinal CD4＋ T cells, and enhanced the frequency of CD4＋ T-cell apoptosis upon challenge with specific antigens. In summary, blocking IL-13 enhances the therapeutic effect of antigen-specific immunotheraov by regulating aDoptosis and thereby enforcing AICD in CD4＋ T cells.