ArticleThe Journal of investigative dermatology2021
Granzyme B Inhibition by Tofacitinib Blocks the Pathology Induced by CD8 T Cells in Cutaneous Leishmaniasis.
Article in The Journal of investigative dermatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions.Pathogens (Basel, Switzerland) · 2024Trial
- Lymphocyte-mediated immune responses to Leishmania infection.Nature reviews. Immunology · 2026Review
- JAK/STAT inhibition reprograms T cell activation and metabolism in inflammatory arthritis patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis.The Journal of investigative dermatology · 2025Article
- Immunomodulatory and regenerative effects of human umbilical cord MSC-EVs in Cutaneous Leishmaniasis.Stem cell research & therapy · 2025Article
- Review
- An overview of host immune responses against Leishmania spp. infections.Human molecular genetics · 2025Review
- Topical AuNPs-Cys-Sm29 gel modulates the course of lesion development in experimental cutaneous leishmaniasis.PLoS neglected tropical diseases · 2025Article
- Oxygen and immunity toInfection and immunity · 2025Review
- CD8 cell-derived granzyme B may be a predictor for coronary artery involvement and MACE in Takayasu arteritis patients.Clinical and experimental immunology · 2025Article
- Senescence-related genes are associated with the immunopathology signature of American tegumentary leishmaniasis lesions and may predict progression to mucosal leishmaniasis.Clinical and experimental immunology · 2025Article
- Chemokines Signature and T Cell Dynamics in Leishmaniasis: Molecular insight and therapeutic application.Expert reviews in molecular medicine · 2024Review
- Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis.Vaccines · 2024Review
- CXCR6JHEP reports : innovation in hepatology · 2024Article
- CCR5 promotes the migration of pathological CD8+ T cells to the leishmanial lesions.PLoS pathogens · 2024Article
- CCR5 promotes the migration of CD8bioRxiv : the preprint server for biology · 2023Article
- NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis.PLoS neglected tropical diseases · 2023Article
- Protection and Pathology inPathogens (Basel, Switzerland) · 2022Review
- Effect of topical berberine in murine cutaneous leishmaniasis lesions.The Journal of antimicrobial chemotherapy · 2022Article
- Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection.Frontiers in immunology · 2022Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In cutaneous leishmaniasis, the immune response is not only protective but also mediates immunopathology. We previously found that cytolytic CD8 T cells promote inflammatory responses that are difficult to treat with conventional therapies that target the parasite. Therefore, we hypothesized that inhibiting CD8 T-cell cytotoxicity would reduce disease severity in patients. IL-15 is a potential target for such a treatment because it is highly expressed in human patients with cutaneous leishmaniasis lesions and promotes granzyme B‒dependent CD8 T-cell cytotoxicity. Here we tested whether tofacitinib, which inhibits IL-15 signaling by blocking Jak3, might decrease CD8-dependent pathology. We found that tofacitinib reduced the expression of granzyme B by CD8 T cells in vitro and in vivo systemic and topical treatment, with tofacitinib protecting mice from developing severe cutaneous leishmaniasis lesions. Importantly, tofacitinib treatment did not alter T helper type 1 responses or parasite control. Collectively, our results suggest that host-directed therapies do not need to be limited to autoimmune disorders and that topical tofacitinib application should be considered a strategy for the treatment of cutaneous leishmaniasis disease in combination with antiparasitic drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.