CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-γ.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Cabral-Marques Otavio, França Tabata Takahashi, Al-Sbiei Ashraf, Schimke Lena Friederike, Khan Taj Ali, Feriotti Claudia, da Costa Tania Alves, Junior Osvaldo Reis, Weber Cristina Worm, Ferreira Janaíra Fernandes, Tavares Fabiola Scancetti, Valente Claudia, Di Gesu Regina Sumiko Watanabe, Iqbal Asif, Riemekasten Gabriela, Amarante-Mendes Gustavo Pessini, Marzagão Barbuto José Alexandre, Costa-Carvalho Beatriz Tavares, Pereira Paulo Vitor Soeiro, Fernandez-Cabezudo Maria J, Calich Vera Lucia Garcia, Notarangelo Luigi D, Torgerson Troy R, Al-Ramadi Basel K, Ochs Hans D, Condino-Neto Antonio
Аннотация
OBJECTIVES: We sought to analyze whether peripheral neutrophils from CD40L-deficient patients display functional defects and to explore the in vitro effects of recombinant human IFN-γ (rhIFN-γ) on neutrophil function.
METHODS: We investigated the microbicidal activity, respiratory burst, and transcriptome profile of neutrophils from CD40L-deficient patients. In addition, we evaluated whether the lack of CD40L in mice also affects neutrophil function.
RESULTS: Neutrophils from CD40L-deficient patients exhibited defective respiratory burst and microbicidal activity, which were improved in vitro by rhIFN-γ but not soluble CD40L. Moreover, neutrophils from patients showed reduced CD16 protein expression and a dysregulated transcriptome suggestive of impaired differentiation. Similar to CD40L-deficient patients, CD40L knockout mice were found to have impaired neutrophil responses. In parallel, we demonstrated that soluble CD40L induces the promyelocytic cell line HL-60 to proliferate and mature by regulating the expression of genes of the same Gene Ontology categories (eg, cell differentiation) when compared with those dysregulated in peripheral blood neutrophils from CD40L-deficient patients.
CONCLUSION: Our data suggest a nonredundant role of CD40L-CD40 interaction in neutrophil development and function that could be improved in vitro by rhIFN-γ, indicating a potential novel therapeutic application for this cytokine.