Rnaseq analysis revealed that Foxp3+ regulatory T cells acquire Th1-like and tissue repair programs during experimental Trypanosoma cruzi infection

CINTIA ARAUJO FURLAN ; VÉRONIQUE ADOUE ; JOANNA FOURQUET ; JIMENA TOSELLO BOARI; CONSTANZA RODRIGUEZ; FERNANDO CANALE; FACUNDO FIOCCA; CRISTIAN BECCARIA; ADRIANA GRUPPI; CAROLINA MONTES; OLIVIER JOFFRE; EVA ACOSTA RODRIGUEZ

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología.; 2016

Sociedad Argentina de inmunología (sai), Sociedad argentina de farmacología experimental (safe), Sociedad argentina de investigación Clínica (SAIC)

Foxp3+CD4+T cells (Tregs) present a dual role during infections as they limit immunopathology but also restrain immunity to the pathogen. Recently, a new role in repairing tissue injury was also ascribed to Tregs. During T. cruzi (Tc) infection, Tregs response has been poorly characterized. Previously, we determined that Tregs become activated during Tc infection, upregulating Foxp3, CD25, GITR and CTLA-4. Moreover, the frequency of Tregs that produce IL-10, TGFbeta and, 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 was analyzed by RNAseq. Briefly, Tregs were purified from the spleenof non-infected (NI) or 22-day-infected (INF) Foxp3-GFP mice, RNA was isolated and cDNA libraries were sequenced. Bioinformaticsanalysis revealed that 5175 genes were differentially expressed in INF Tregs compared to NI Tregs. In agreement with our previousresults, RNAseq further confirmed the activated status of INF Tregs as these cells showed increased amounts of transcripts for suppressive and activation markers. Remarkably, Tbx21 and Areg (coding for amphiregulin) appear among the most upregulated genes in INF Tregs. A more exhaustive analysis showed that not only Tbx21 but also other genes related to Th1 responses (e.g., Ifng, Cxcr3, Stat1, Il12rb2 and Ifngr1) were also significantly upregulated, suggesting the acquisition of a Th1-like profile by INF Tregs. Of note, in addition to Areg, INF Tregs upregulated other genes associated with tissue repair properties of muscle and lung Tregs, including Il18r1, Il18rap, Neb, Ccr2, Il10, Gzmb, Itgae and Havcr2. As previously reported for spleen Tregs, INF Tregs showed no changes in the expression of St2 (coding for IL-33 receptor) compared to NI Tregs. These results suggest that during Tc infection, Tregs acquire a program specialized in controlling Th1 immune responses and promoting tissue repair.