RNASEQ ANALYSIS REVEALED THAT FOXP3+ REGULATORY T CELLS ACQUIRE TH1-LIKE AND TISSUE REPAIR PROGRAMS DURING EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION.

ARAUJO FURLAN, CINTIA; ADOUE, VERONIQUE; FOURQUET, JOANA; TOSELLO BOARI, JIMENA; RODRIGUEZ, CONSTANZA; CANALE, FERNANDO; BECCARIA, CRISTIAN G; FIOCCA VERNENGO, FACUNDO; GRUPPI, ADRIANA; MONTES, CAROLINA L.; JOFFRE, OLIVIER; ACOSTA RODRIGUEZ E V

Mar del Plata

Congreso; LXIV Reunión científica anual de la Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE.; 2016

Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE.

024 (890) RNASEQ ANALYSIS REVEALED THAT FOXP3+REGULATORY T CELLS ACQUIRE TH1-LIKE AND TISSUEREPAIR PROGRAMS DURING EXPERIMENTALTRYPANOSOMA CRUZI INFECTIONCintia Araujo Furlan1, Véronique Adoue2, Joanna Fourquet2,Jimena Tosello Boari1, Constanza Rodriguez1, FernandoCanale1, Facundo Fiocca1, Cristian Beccaria1, AdrianaGruppi1, Carolina Montes1, Olivier Joffre2, Eva AcostaRodriguez1.1CIBICI-CONICET, Departamento de Bioquímica Clínica,Facultad de Ciencias Químicas, UNC, Córdoba, Argentina.2Centre de Physiopathologie de Toulouse Purpan,Toulouse, France.Foxp3+ CD4+ T cells (Tregs) present a dual role during infectionsas they limit immunopathology but also restrain immunity to the pathogen.Recently, a new role in repairing tissue injury was also ascribedto Tregs. During T. cruzi (Tc) infection, Tregs response has beenpoorly characterized. Previously, we determined that Tregs becomeactivated during Tc infection, upregulating Foxp3, CD25, GITR andCTLA-4. Moreover, the frequency of Tregs that produce IL-10, TGFbetaand, interestingly, IFN-gamma, was increased by the infection.Here, our aim was to examine the emergence of specialized Tregspopulations during Tc infection. For this, Tregs transcriptome wasanalyzed by RNAseq. Briefly, Tregs were purified from the spleenof non-infected (NI) or 22-day-infected (INF) Foxp3-GFP mice, RNAwas isolated and cDNA libraries were sequenced. Bioinformaticsanalysis revealed that 5175 genes were differentially expressed inINF Tregs compared to NI Tregs. In agreement with our previousresults, RNAseq further confirmed the activated status of INF Tregsas these cells showed increased amounts of transcripts for suppressiveand activation markers. Remarkably, Tbx21 and Areg (codingfor amphiregulin) appear among the most upregulated genes in INFTregs. A more exhaustive analysis showed that not only Tbx21 butalso other genes related to Th1 responses (e.g., Ifng, Cxcr3, Stat1,Il12rb2 and Ifngr1) were also significantly upregulated, suggestingthe acquisition of a Th1-like profile by INF Tregs. Of note, in additionto Areg, INF Tregs upregulated other genes associated with tissuerepair properties of muscle and lung Tregs, including Il18r1, Il18rap,Neb, Ccr2, Il10, Gzmb, Itgae and Havcr2. As previously reported forspleen Tregs, INF Tregs showed no changes in the expression ofSt2 (coding for IL-33 receptor) compared to NI Tregs. These resultssuggest that during Tc infection, Tregs acquire a program specializedin controlling Th1 immune responses and promoting tissue repair.