Increased amphiregulin expression by CD4⁺ T cells from individuals with asymptomatic Leishmania donovani infection

Abstract

Objectives There is an urgent need to be able to identify individuals with asymptomatic Leishmania donovani infection, so their risk of progressing to VL and transmitting parasites can be managed. This study examined transcriptional markers expressed by CD4+ T cells that could distinguish asymptomatic individuals from endemic controls and visceral leishmaniasis (VL) patients. Methods CD4+ T cells were isolated from individuals with asymptomatic L. donovani infection, endemic controls and VL patients. RNA was extracted and RNAseq employed to identify differentially expressed genes. The expression of one gene and its protein product during asymptomatic infection were evaluated. Results Amphiregulin (AREG) was identified as a distinguishing gene product in CD4+ T cells from individuals with asymptomatic L. donovani infection, compared to VL patients and healthy endemic control individuals. AREG levels in plasma and antigen‐stimulated whole‐blood assay cell culture supernatants were significantly elevated in asymptomatic individuals, compared to endemic controls and VL patients. Regulatory T (Treg) cells were identified as an important source of AREG amongst CD4+ T‐cell subsets in asymptomatic individuals. Conclusion Increased Treg cell AREG expression was identified in individuals with asymptomatic L. donovani infection, suggesting the presence of an ongoing inflammatory response in these individuals required for controlling infection and that AREG may play an important role in preventing inflammation‐induced tissue damage and subsequent disease in asymptomatic individuals.

Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors

“…The hybrid population of T H1 and T H2 cells was characterized by the expression of AREG, GATA3, PTGDR2, and CXCR3, known features of helper CD4 T cells ( Figures 2 A and S2 A). 16 , 17 , 18 , 19 Cluster 14 expressed genes that were mainly involved in T H17 responses (further details in Figure 4 ). As expected, the majority of the peripheral CD4 T cells resembled naive cells (cluster 22), characterized also by the expression of the transcription factors TCF7 and LEF1 and the chemokine receptor CCR7.…”

Altered IL-7 signaling in CD4+ T cells from patients with visceral leishmaniasis

“…Flow Jo version 10 software (Tree Star, BD) was used to analyze the FACS data. CD4 + T cell subsets were defined as Treg (CD25 + , CD127 -), Tem (CD45RA +/-, CCR7 -), Th (Tem-CXCR5), Th17_Th22 (CCR6 + , CCR4 + ), Th1_Th2 (Th-CCR6, CCR4 +/-), Th1 (Th1_Th2-CCR4, CXCR3 + ), Th2 (Th1_Th2-CXCR3 CCR4 + ), Th9 (Th-CCR4, CCR6 + ) [23][24][25][26]. CD4 + T cell subsets were defined as previously PLOS NEGLECTED TROPICAL DISEASES reported by us and others (References [18,[23][24][25][26]), and the gating strategy employed was as we previously described (references [18,25]).…”

“…CD4 + T cell subsets were defined as Treg (CD25 + , CD127 -), Tem (CD45RA +/-, CCR7 -), Th (Tem-CXCR5), Th17_Th22 (CCR6 + , CCR4 + ), Th1_Th2 (Th-CCR6, CCR4 +/-), Th1 (Th1_Th2-CCR4, CXCR3 + ), Th2 (Th1_Th2-CXCR3 CCR4 + ), Th9 (Th-CCR4, CCR6 + ) [23][24][25][26]. CD4 + T cell subsets were defined as previously PLOS NEGLECTED TROPICAL DISEASES reported by us and others (References [18,[23][24][25][26]), and the gating strategy employed was as we previously described (references [18,25]). Details of all antibodies used in this study are described in S2 Table.…”

Application of amphiregulin in IVM culture of immature human oocytes and pre-insemination culture for COCs in IVF cycles

“…In 1988, amphiregulin (AR), an epidermal growth factor (EGF)-like growth factor, was found to bind only to the EGF receptor (EGFR) and regulate the growth of MCF-7 breast tumor cells in a serum-free medium ( 1 ). After binding to EGFR, AR activates a basic cascade of intracellular signaling in the cell cycle ( 2 , 3 ). AR activation is driven by multiple factors, including cytokines, hormones, and growth factors ( 4 ).…”