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A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Fibroblast activation protein is dispensable in the anti-influenza immune response in mice
Sioh-Yang Tan1,2, Sumaiya Chowdhury2,3, Natasa Polak2,3
1Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
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.
Insights
Fibroblast activation protein alpha (FAP) is a dual peptidase. FAP deficiency did not impair immune cell development or anti-influenza responses in mice, suggesting it is dispensable for adaptive immunity against this virus.
Area of Science:
- Immunology
- Protease biochemistry
Background:
- Fibroblast activation protein alpha (FAP) is a serine protease with dual enzymatic activities.
- FAP is upregulated in cancer-associated fibroblasts and during tissue remodeling, but its role in the immune system, particularly in infection, is largely unknown.
- While FAP knockout mice are viable, their immune system function requires further investigation.
Purpose of the Study:
- To investigate the role of FAP in immune cell development and function.
- To determine the necessity of FAP in adaptive immune responses during viral infection, specifically influenza.
Main Methods:
- Generation and characterization of FAP-deficient mice.
- Assessment of major immune cell populations (T cells, B cells, dendritic cells, neutrophils) in FAP knockout mice.
- Intranasal challenge with influenza virus in FAP-deficient and wildtype mice.
- Analysis of viral pathology, immune cell responses, and gene expression in the lungs and lymph nodes.
Main Results:
- FAP knockout mice exhibited normal generation and maintenance of major immune cell populations.
- FAP mRNA levels increased in the lungs and draining lymph nodes following influenza infection.
- FAP-deficient mice displayed similar pathological outcomes and supported normal anti-influenza T and B cell responses compared to wildtype controls.
- No compensatory upregulation of other dipeptidyl peptidase 4 (DPP4) family members was observed in FAP-deficient mice during influenza infection.
Conclusions:
- Fibroblast activation protein alpha (FAP) is not essential for the development and maintenance of key immune cell populations.
- FAP is dispensable for mounting an effective adaptive immune response against influenza virus infection in mice.
- These findings highlight a specific role for FAP in certain physiological contexts, distinct from its function in anti-viral immunity.
