Fibroblast activation protein is dispensable in the anti-influenza immune response in mice.
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.
Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.|Sydney Medical School, The University of Sydney, New South Wales, Australia.
Sioh-Yang
http://orcid.org/0000-0002-0151-7365
SY
Tan
Sydney Medical School, The University of Sydney, New South Wales, Australia.|Molecular Hepatology Laboratory, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
Sumaiya
S
Chowdhury
Sydney Medical School, The University of Sydney, New South Wales, Australia.|Molecular Hepatology Laboratory, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
Natasa
N
Polak
Sydney Medical School, The University of Sydney, New South Wales, Australia.|Molecular Hepatology Laboratory, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
Mark D
MD
Gorrell
Immune Imaging Program, Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.|Sydney Medical School, The University of Sydney, New South Wales, Australia.|Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Wolfgang
W
Weninger
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D004195:Disease Models, Animal; D010450:Endopeptidases; D018093:Gelatinases / Q000235:genetics* / Q000378:metabolism; D007109:Immunity; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D010641:Phenotype; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
D015415:Biomarkers; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha