Dataset Information

Impaired respiratory burst contributes to infections in PKCδ-deficient patients.

ABSTRACT: Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40phox normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients' circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKCδ in activation of the NADPH oxidase complex. Our findings thus show that patients with PKCδ deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype.

SUBMITTER: Neehus AL

PROVIDER: S-EPMC8288504 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impaired respiratory burst contributes to infections in PKCδ-deficient patients.

Neehus Anna-Lena AL Moriya Kunihiko K Nieto-Patlán Alejandro A Le Voyer Tom T Lévy Romain R Özen Ahmet A Karakoc-Aydiner Elif E Baris Safa S Yildiran Alisan A Altundag Engin E Roynard Manon M Haake Kathrin K Migaud Mélanie M Dorgham Karim K Gorochov Guy G Abel Laurent L Lachmann Nico N Dogu Figen F Haskologlu Sule S İnce Erdal E El-Benna Jamel J Uzel Gulbu G Kiykim Ayca A Boztug Kaan K Roderick Marion R MR Shahrooei Mohammad M Brogan Paul A PA Abolhassani Hassan H Hancioglu Gonca G Parvaneh Nima N Belot Alexandre A Ikinciogullari Aydan A Casanova Jean-Laurent JL Puel Anne A Bustamante Jacinta J

The Journal of experimental medicine 20210715 9

Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and mono ...[more]

PMID: 34264265

Similar Datasets

Project description:IntroductionB7-H4 is overexpressed in colorectal cancer (CRC) and plays an important role in tumor growth and immunosuppression. However, the exact mechanism that regulates B7-H4 expression remains largely unknown. Here, we investigated whether protein kinase C δ (PKCδ) regulates the expression of B7-H4 in CRC.MethodsBy using immunohistochemical (IHC) and immunofluorescence (IF) staining, we analyzed the expression of B7-H4 and phospho-PKCδ (p-PKCδ) in 225 colorectal tumor samples and determined the clinical significance of the expression patterns. In vitro experiments were performed with the CRC cell lines HCT116 and SW620 to detect the effect of PKCδ activation on B7-H4 expression, and xenograft-bearing mice were treated with rottlerin to monitor the expression of B7-H4 and tumor metastasis.ResultsThe B7-H4 expression level was significantly correlated with the p-PKCδ level (r = 0.378, P < 0.001) in tumor tissues. Coexpression of p-PKCδ and B7-H4 was significantly associated with moderate/poor differentiation (P = 0.024), lymph node metastasis (P = 0.001) and advanced Dukes' stage (P = 0.002). Western blot analysis showed that Phorbol-12-Myristate-13-Acetate (TPA) increased B7-H4 expression in a concentration-dependent manner and that rottlerin abrogated the TPA-induced increase in B7-H4 expression. The protein levels of B7-H4 and p-STAT3 were significantly reduced by a PKCδ-specific siRNA. Moreover, the STAT3 inhibitor cryptotanshinone significantly decreased the B7-H4 protein level in CRC cells. Knockdown of B7-H4 or PKCδ suppressed cell migration and motility. Rottlerin also inhibited B7-H4 expression and tumor metastasis in vivo.ConclusionThe B7-H4 expression level is significantly correlated with the p-PKCδ level and tumor metastasis in CRC samples. B7-H4 expression is upregulated by STAT3 activation via PKCδ and plays roles in PKCδ-induced cancer cell motility and metastasis, suggesting that the PKCδ/STAT3/B7-H4 axis may be a potential therapeutic target for CRC.

Dataset Information

Impaired respiratory burst contributes to infections in PKCδ-deficient patients.

Publications

Impaired respiratory burst contributes to infections in PKCδ-deficient patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets