Biology subjects

Araujo Furlan, C. L.

Publications and source records attributed to Araujo Furlan, C. L..

4 recordsLinked to original sources

bioRxiv2026

Dual Th1 and tissue-repair Treg cells accumulate in skeletal muscle preserving tissue integrity during infection

Chronic infections require mechanisms that limit tissue damage while preserving pathogen control, yet the contribution of regulatory T (Treg) cells to this balance remains unclear. In this study, we characterized Treg cell responses during a chronic parasitic infection using experimental Trypanosoma cruzi infection as a model of persistent low-level parasitism and chronic tissue inflammation. We found that, although Treg cell numbers decline in the spleen, they accumulate in parasite-affected tissues such as skeletal muscle, where they adopt a combined Th1-associated and tissue-repair program. Systemic Treg cell depletion had limited impact on immune and disease-associated parameters, whereas local depletion in skeletal muscle exacerbated tissue damage and increased parasite burden. Moreover, transient systemic perturbation of Treg cells during the acute phase impaired their long-term accumulation in skeletal muscle, resulting in increased tissue damage and parasite burden during chronic infection. Additionally, accumulation of reparative Treg cells in skeletal muscle was impaired in the absence of ST2. Together, these findings identify a tissue-adapted Treg cell population that integrates inflammatory and reparative programs to preserve skeletal muscle integrity during chronic parasitic infection. SUMMARYChronic parasite infection drives the emergence of tissue-adapted regulatory T cells that integrate Th1-associated and tissue-repair programs. These cells accumulate in skeletal muscle, where they preserve tissue integrity while contributing to microbial control, highlighting the dynamic specialization of Treg cells across disease stages.

immunology↗

bioRxiv2022

Interleukin-17 signaling influences CD8+ T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells

The role of IL-17 mediated immune responses in cancer is conflicting as pre-clinical and clinical results show tumor-promoting as wel as tumor-repressing functions. Herein, we used syngeneic tumor models from different tissue origins as a tool to evaluate the role of IL-17 signaling in cancer progression, dissecting the effects in cancer cell growth and tumor immunity. We show that absence of IL-17RA or IL-17A/F expression in the host has contrasting effects in the in vivo growth of different tumor types. We observed that lack of IL-17A/F-IL-17RA signaling in host cells changed the expression pattern of several mediators within the tumor microenvironment in a cancer-type specific manner. Deficiencies in host IL-17RA or IL-17A/F expression resulted in reduced antitumor CD8+ T cell immunity in all cancer models and in tumor-specific changes in several lymphoid cell populations. These findings were associated to particular patterns of expression of cytokines (IL-17A and IL-17F) and receptor subunits (IL-17RA, IL-17RC and IL-17RD) of the IL-17 family in the injected tumor cell lines that, in turn, dictated tumor cell responsiveness to IL-17. We identified IL-17RC as an important determinant of the IL-17-mediated transcriptional response in tumor cells and; consequently, as a predictive biomarker of the overall effect of IL-17 signaling in tumor progression. Our findings contribute to unraveling the molecular mechanisms underlying the divergent activities of IL-17 in cancer and provide rational targets for immunotherapies based on personalized approaches.

immunology↗

bioRxiv2019

CD8+ T cell immunity is compromised by anti-CD20 treatment and rescued by IL-17A

Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8+ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+ T cells at 20 days postinfection. Anti-CD20 injection decreased the number of effector and memory CD8+ T cells and reduced the frequency of proliferating and cytokine producing CD8+ T cells. Accordingly, infected anti-CD20-treated mice presented a lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8+ T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened an established CD8+ T cell response, indicating that B cells were involved in the maintenance rather than the induction of CD8+ T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of IL-6- and IL-17A-producing cells, and only rIL-17A injection partially restored the CD8+ T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8+ T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly.\n\nImportanceMonoclonal antibody targeting the CD20 antigen on B cells is used to treat the majority of Non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections and activation of viruses from latency. Here, using the infection murine model with the intracellular parasite Trypanosoma cruzi, we report that anti-CD20 treatment not only affects B cell response but also CD8+ T cells, the most important immune effectors involved in control of intracellular pathogens. Anti-CD20 treatment, directly or indirectly, affects cytotoxic T cell number and function and this deficient response was rescued by the cytokine IL-17A. The identification of IL-17A as the cytokine capable of reversing the poor response of CD8+ T cells provide information about a potential therapeutic treatment aimed at enhancing defective immunity induced by B cell depletion.

immunology↗

bioRxiv2018

IL-17RA-signaling modulates CD8+ T cell survival and exhaustion during Trypanosoma cruzi infection

The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes and their survival and appropriate response is orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. Absence of IL-17RA and IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signaling in vivo increased apoptosis of parasite-specific CD8+ T cells while recombinant IL-17 in vitro down-regulated the pro-apoptotic protein BAD and promoted activated CD8+ T cell survival. Phenotypic, functional and trancriptomic profiling showed that T. cruzi-specific CD8+ T cells arising in IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magnitude of CD8+ T cell responses and parasite control in these mice. Adoptive transfer experiments established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells. Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity to T. cruzi.

immunology↗