PICK OF THE MONTH (by Emilio Jirillo, University of Bari, Bari, Italy)


Resolvin D1 and aspirin-triggered resolving D1 promote resolution of allergic airways responses
Rogerio PA, Haworth O, Croze R, Oh SF, Uddin M, Carlo T, Pfeffer MA, Priluck R, Serhan CN, Levy BD
The Journal of Immunology 189: 1983-1991, 2012.

The effects of resolvin D1 (RvD1) and aspirin-triggered RvD1 (AT-RvD1) on the allergic airway responses were evaluated in mice before and after aerosol allergen challenge.RvD1 and mostly AT-RvD1 were able to decrease airway eosinophilia and mucus metaplasia.

AT-RvD1 was more resistant to metabolic inactivation by macrophages, also enhancing phagocytosis of IgG-ova-coated beads both in vitro and in vivo. This last effect promoted macrophage clearance of allergen, thus suggesting that resolvins may represent potential proresolving agents in allergic responses.

Blocking Fc alpha Receptor I on granulocytes prevents tissue damage induced by IgA autoantibodies
Van der Steen LP, Bakema JE, Sesarman A, Florea F, Tuk CW, Kirtschig G, Hage JJ, Sitaru C, van Egmond M
The Journal of Immunology 189:1594-1601, 2012.

Evidence has been provided that cross-linking of the granulocyte IgA FcR (Fc alpha RI) by IgA leads to a chemotactic response , thus enhancing recruitment of granulocytes to IgA deposits, ultimately causing tissue damage in IgA-mediated diseases. In this study, authors demonstrated colocalization of Fc alpha RI-positive granulocyte infiltrates with IgA in cryosections of skin in patients suffering from skin-blistering disease. Furthermore, granulocyte migration to IgA deposits injected in human skin explants was reported as well as in murine skin of Fc alpha RI transgenic mice in vivo. Blocking FC alpha RI reduced tissue damage, thus suggesting that these pathological events are dependent on the interaction of IgA autoantibodies with Fc alpha RI.

Programming of Regulatory T Cells from pluripotent stem cells and prevention of autoimmunity
Haque R, Lei F, Xiong X, Bian Y, Zhao B, Wu Y, Song J
The Journal of Immunology 189: 1228-1236, 2012.

This study was designed to generate regulatory T (TREG) cells from induced pluripotent stem cells (iPS) via ligation of a notch ligand and transduction of the gene Foxp3. Adoptive transfer of iPS-derived TREG cells was able to suppress immune responses and decrease murine arthritis development. TREG cells performed their suppressive function via release of Transforming Growth Factor beta and Interleukin-10. These findings provide a novel therapeutic approach for treating autoimmune diseases.

T cell apoptosis and induction of Foxp3+ Regulatory T cells underlie the therapeutic efficacy of CD4 bockade in experimental autoimmune encephalomyelitis
Duarte J, Carrié N, Oliveira VG, Almeida C, Agua-Doce A, Rodrigues L, Simas JP, Mars LT, Graca L
The Journal of Immunology 189: 1680-1688, 2012.

Evidence has been provided that CD4 blockade can prevent experimental autoimmune encephalomyelitis (EAC) in mice. Anti CD4 monoclonal antibody (mAb) was able to inhibit the proliferation of naïve antigen-specific T cells as well as differentiation of Th1 and Th17 cells. At the same time, this mAb promoted the differentiation of Foxp3+ Regulatory T cells.

In conclusion, targeting with mAbs CD4 may represent a novel approach for treating EAC and other autoimmune diseases.

Targeting Stat3 induces senescence in tumor cells and elicits prophylactic and therapeutic immune responses against breast cancer growth mediated by NK cells and CD4+ T cells
Tkach M, Coria L, Rosemblit C, Rivas M, Proietti CJ, Diaz Flaque MC, Beguelin W, Frahm I, Charreau EH, Cassataro J, Elizalde PV, Schillaci R

The Journal of Immunology 189: 1162-1172, 2012.

Stat3 activation in tumor cells has been shown to mediate tumor immune evasion and, therefore, ablating Stat3 signaling in breast cancer cells may retard cancer growth and metastasis. In this study, mice were immunized with irradiated cancer cells transfected with a dominant Stat3 vector (Stat3Y705F). Prophylactic administration of transfected breast cancer cells with the Stat3 vector not only inhibited primary tumor growth but also metastasis decreased by 90% via an immune mechanism mediated by CD4+ cells and NK cells. Also therapeutic immunization with Stat3Y705F-breast cancer cells retarded tumor growth and formation of metastasis, while favoring tumor cell differentiation. In general terms, ablation of Stat3 in tumors seems to induce a cellular senescence program, thus suggesting a potential approach of anticancer therapy.

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