Table 1.
Conditional knockout mice demonstrate critical role of fibroblast immune function in barrier tissue disease.
| Deletion (fl/fl) | Targeting strategy (Cre) | Tissue | Disease model | Outcome | Reference |
|---|---|---|---|---|---|
| ll4ra | Pdgfra + | Skin | Atopic dermatitis (OVA & papain) | Reduced immune fibroblast expansion | Boothby 2021 |
| lkbkb | Prrx1+ | Skin | Atopic dermatitis (none) | Increased Th2 inflammation | Ko 2022 |
| lkbkb | Col1a2+ | Skin | Atopic dermatitis (none) | Increased Th2 inflammation | Ko 2022 |
| lfngr1 | Pdgfra+ | Skin | Vitiligo (melanoma-Treg induced) | Reduced depigmentation | Xu 2022 |
| lkbkb | Col6a1+ | Intestine | Colitis-associated cancer (DSS/AOM) | Reduced cancer development | Koliaraki 2015 |
| Tpl2 | Col6a1+ | lntestine | Colitis-associated cancer (DSS/AOM) | Increased cancer development | Koliaraki 2012 |
| Stat3 | Col6a1+ | Intestine | Colitis-associated cancer (DSS/AOM) | Reduced cancer development | Heichler 2020 |
| Myd88 | Acta2+ | Intestine | Colitis-associated cancer (DSS/AOM) | Reduced cancer development | Yuan 2021 |
| Ptgs2 | Twist2+ | Intestine | Colitis-associated cancer (DSS/AOM) | Reduced cancer development | Gao 2021 |
| Tlr4 | Twist2+ | lntestine | Colitis, acute (DSS) | Increased disease severity | Gao 2021 |
| Ptgs2 | Twist2+ | lntestine | Colitis, acute (DSS) | Increased disease severity | Gao 2021 |
| Mapk14 | Twist2+ | Intestine | Colitis, acute (DSS) | Increased disease severity | Gao 2021 |
| lkkb | Col6a1+ | Intestine | Colitis, acute (DSS) | Reduced disease severity | Koliaraki 2015 |
| Tpl2 | Col6a1+ | Intestine | Colitis, acute (DSS) | Increased disease severity | Roulis 2014 |
| Myd88 | Acta2+ | Intestine | Colitis, acute (DSS) | Increased disease severity | Yuan 2021 |
| Myd88 | Col1a2+ | Intestine | Colitis, acute (DSS) & homeostasis | Reduced fibroblast PD-L1 & increased IFNγ | Beswick 2014 |
| Myd88 | Acta2+ | Intestine | Colitis, chronic (DSS) | Reduced disease severity | Zhao 2020 |
| Tnfsf11 | Twist2+ | Intestine | Homeostasis | Reduced antigen sampling and microbial diversity | Nagashima 2017 |
| Tnfrsf1a | All cells except Col6a1+ | Intestine | Ileitis (TNFα over-expression) | Fibroblast TNFα signaling sufficient for pathology | Armaka 2008 |
| Myd88 | Col6a1+ | lntestine | Spontaneous tumorigenesis (ApcMin) | Reduced cancer development | Koliaraki 2019 |
| Tlr4 | Col6a1+ | Intestine | Spontaneous tumorigenesis (ApcMin) | Reduced cancer development | Kdiaraki 2019 |
| Ptgs2 | Col6a1+ | Intestine | Spontaneous tumorigenesis (ApcMin) | Reduced cancer development | Roulis 2020 |
| Tnfrsf1a | All cells except Col6a1+ | Intestine | Viral infection (Coronavirus) | Reduced antiviral lgA production | Prados 2021 |
| ll15 | Ccl19+ | Intestine | Viral infection (Mouse Hepatitis Virus) | Reduced ILC1s | Gil-Cruz 2016 |
| Myd88 | Ccl19+ | Intestine | Viral infection (Mouse Hepatitis Virus) | Increased disease severity | Gil-Cruz 2016 |
| lgf1 | Gli1+ | Lung | Bacterial infection (S. pneumoniae) | Reduced protection from infection | Oherle 2020 |
| ll17ra | Twist2+ | Lung | Bacterial vaccination (K. pneumoniae) | Reduced vaccine efficacy | lwanaga 2021 |
| ll17ra | Col1a2+ | Lung | Bacterial vaccination (K. pneumoniae) | Reduced vaccine efficacy | Iwanaga 2021 |
| ll33 | Gli1+ | Lung | Helminth infection (N. brasiliensis) | Reduced Th2 cell development | Dahlgren 2019 |
| ll33 | Ccl19+ | Lung | Viral infection (Adenovirus) | Reduced infiating memory CD8 T cell function | Cupovic 2021 |
DSS, Dextran sodium sulfate; AOM, Azaxymethane.