Dey, Nidhi S, Dey, Shoumit orcid.org/0000-0003-2655-9921, Brown, Naj et al. (11 more authors) (2025) IL-32-producing CD8+ memory T cells define immunoregulatory niches in human cutaneous leishmaniasis. Journal of Clinical Investigation. 182040. ISSN 1558-8238
Abstract
Human cutaneous leishmaniasis (CL) is characterized by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome, but the cellular and molecular niches that facilitate IC molecule expression during leishmaniasis are ill defined. In Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) were enriched in skin lesions, and reduced PD-L1 expression early after treatment initiation was predictive of a cure rate following antimonial therapy. Here, we used spatial cell interaction mapping to identify IL-32-expressing CD8+ memory T cells and Tregs as key components of the IDO1/PD-L1 niche in Sri Lankan patients with CL and in patients with distinct forms of dermal leishmaniasis in Brazil and India. Furthermore, the abundance of IL-32+ cells and IL-32+CD8+ T cells at treatment initiation was negatively correlated with the rate of cure in Sri Lankan patients. This study provides insights into the spatial mechanisms underpinning IC expression during CL and offers a strategy for identifying additional biomarkers of treatment response.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025, Dey et al. |
Keywords: | Humans,CD8-Positive T-Lymphocytes/immunology,Leishmaniasis, Cutaneous/immunology,Male,Female,Adult,Interleukins/immunology,Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology,Immunologic Memory,Middle Aged,T-Lymphocytes, Regulatory/immunology,B7-H1 Antigen/immunology,Memory T Cells/immunology,Sri Lanka |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 19 May 2025 13:00 |
Last Modified: | 19 May 2025 13:00 |
Published Version: | https://doi.org/10.1172/JCI182040 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1172/JCI182040 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:226850 |
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