Abstract
Fibroblast activation protein alpha (FAP) is a unique dual peptidase of the S9B serine protease family, being capable of both dipeptidyl peptidase and endopeptidase activities. FAP is expressed at low level in healthy adult organs including the pancreas, cervix, uterus, submaxillary gland and the skin, and highly upregulated in embryogenesis, chronic inflammation and tissue remodelling. It is also expressed by cancer-associated stromal fibroblasts in more than 90% of epithelial tumours. FAP has enzymatic and non-enzymatic functions in the growth, immunosuppression, invasion and cell signalling of tumour cells. FAP deficient mice are fertile and viable with no gross abnormality, but little data exist on the role of FAP in the immune system. FAP is upregulated in association with microbial stimulation and chronic inflammation, but its function in infection remains unknown. We showed that major populations of immune cells including CD4+ and CD8+ T cells, B cells, dendritic cells and neutrophils are generated and maintained normally in FAP knockout mice. Upon intranasal challenge with influenza virus, FAP mRNA was increased in the lungs and lung-draining lymph nodes. Nonetheless, FAP deficient mice showed similar pathologic kinetics to wildtype controls, and were capable of supporting normal anti-influenza T and B cell responses. There was no evidence of compensatory upregulation of other DPP4 family members in influenza-infected FAP-deficient mice. FAP appears to be dispensable in anti-influenza adaptive immunity.
Highlights
Fibroblast activation protein alpha (FAP), previously known as seprase, is a member of the S9B serine protease family, which comprises dipeptidyl peptidases uniquely capable of cleaving a post-proline peptide bond [1, 2]
While DPP4 knockout mice have altered proportions of CD4 T cells, NK cells and NKT cells, altered cytokine and antibody production [61] and heightened response to allergenic sensitisation [62], we found no difference between FAP knockout and wildtype mice in CD4+ and CD8+ T cells, B cells, dendritic cells and neutrophils
T cells and dendritic cells in FAP knockout mice were phenotypically indistinguishable from their wildtype counterparts
Summary
Fibroblast activation protein alpha (FAP), previously known as seprase, is a member of the S9B serine protease family, which comprises dipeptidyl peptidases uniquely capable of cleaving a post-proline peptide bond [1, 2]. The members of this family include DPP4/CD26, DPP8 and DPP9. FAP has closest homology to DPP4, with which it shares 51% identity in amino acid sequence in the mouse, but FAP is unique in the DPP4 family as it is an endopeptidase[3]. Immune response in FAP knockout mice cooperfoundation.org.au) (MDG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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