Dos-Santos Júlio Souza, Firmino-Cruz Luan, Oliveira-Maciel Diogo, da Fonseca-Martins Alessandra Marcia, Ramos Tadeu Diniz, Nunes-Sousa Letícia, Bittencourt Dos Santos Igor, Pedro Soares Rodrigo, Claudio Oliveira Gomes Daniel, Mengel José, Silva-Santos Bruno, de Matos Guedes Herbert Leonel
Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil.
J Leukoc Biol. 2025 Mar 14;117(3). doi: 10.1093/jleuko/qiae251.
γδ T cells play diverse roles in immune responses, producing either interleukin (IL)-17A or interferon γ (IFN-γ). Here, we investigated the impact of this functional dichotomy on cutaneous leishmaniasis. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, Vγ4+ γδ T cells are the main source of IL-17A. In type 1 IFN receptor-deficient (A129) mice with heightened susceptibility, there is an increased frequency of IL-17A-producing γδ T cells. L. amazonensis' lipophosphoglycan induces these IL-17A-producing γδ T cells. Notably, C57BL/6 mice deficient in γδ T cells or IL-17 receptor exhibit smaller lesions, indicating a pathogenic role of IL-17A-producing γδ T cells in cutaneous leishmaniasis. Conversely, adoptive transfer of fluorescence-activated cell sorting (FACS)-sorted γδ T cells lead to an accumulation of IFN-γ-producing γδ T cells, associated with control of lesion development. On the other hand, adoptive transfer of FACS-sorted IFN-γ-deficient γδ T cells abolished the control of lesion development. These data demonstrate a pathophysiological dichotomy in which IL-17A-producing γδ T cells promote pathogenesis, while IFN-γ-producing γδ T cells offer therapeutic potential in cutaneous leishmaniasis.
γδ T细胞在免疫反应中发挥多种作用，可产生白细胞介素（IL）-17A或干扰素γ（IFN-γ）。在此，我们研究了这种功能二分法对皮肤利什曼病的影响。我们证明，在易感染亚马逊利什曼原虫的Sv129小鼠中，Vγ4 + γδ T细胞是IL-17A的主要来源。在易感性增强的1型干扰素受体缺陷（A129）小鼠中，产生IL-17A的γδ T细胞频率增加。亚马逊利什曼原虫的脂磷壁酸可诱导这些产生IL-17A的γδ T细胞。值得注意的是，缺乏γδ T细胞或IL-17受体的C57BL / 6小鼠表现出较小的病变，表明产生IL-17A的γδ T细胞在皮肤利什曼病中具有致病作用。相反，荧光激活细胞分选（FACS）分选的γδ T细胞的过继转移导致产生IFN-γ的γδ T细胞积累，这与病变发展的控制有关。另一方面，FACS分选的IFN-γ缺陷γδ T细胞的过继转移消除了对病变发展的控制。这些数据证明了一种病理生理二分法，即产生IL-17A的γδ T细胞促进发病机制，而产生IFN-γ的γδ T细胞在皮肤利什曼病中具有治疗潜力。
