TY - JOUR
T1 - γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
AU - Quintana, Juan F.
AU - Sinton, Matthew C.
AU - Chandrasegaran, Praveena
AU - Lestari, Agatha Nabilla
AU - Heslop, Rhiannon
AU - Cheaib, Bachar
AU - Ogunsola, John
AU - Ngoyi, Dieudonne Mumba
AU - Swar, Nono-Raymond Kuispond
AU - Cooper, Anneli
AU - Mabbott, Neil
AU - Coffelt, Seth B.
AU - MacLeod, Annette
N1 - Funding Information:
We thank Julie Galbraith and Pawel Herzyk (Glasgow Polyomics, University of Glasgow) for their support with library preparation and sequencing. Similarly, we would like to thank the technical staff at the University of Glasgow Biological Services for their assistance in maintaining optimal husbandry conditions and comfort for the animals used in this study. We would also like to thank Frazer Bell, Lynn Stevenson, and the rest of the University of Glasgow Veterinary school histopathology service for the technical assistance with histological advice and preparations. We thank the Maria Kasper Lab (Karolinska Institutet, Sweden) for their advice on single cell skin dissociation, and Rebecca O’Brien (National Jewish Health, USA) for providing the Vγ4/6 mice. We also thank Shinya Hatano and Yasunobu Yoshikai (Kyushu University, Fukuoka, Japan) for providing the Vγ6 antibody. We thank Dr Jean Rodgers for the work conducted under her Home Office Animal License (PPL No. PC8C3B25C). This work was funded by a Sir Henry Wellcome postdoctoral fellowship (221640/Z/20/Z to JFQ), a Wellcome Trust FutureScope grant (104111/Z/14/Z Wellcome Centre for Integrative Parasitology to JFQ), a University of Glasgow Lord Kelvin Adam Smith Leadership Fellowship (to JFQ), and a Wellcome Trust Senior Research fellow (209511/Z/17/Z to AML). RH is a Wellcome Trust PhD student (Wellcome Trust 218518/Z/19/Z). MCS, PC, JO, AC, and NRK are supported by a Wellcome Trust Senior Research fellowship (209511/Z/17/Z) awarded to AML. JO is also supported by a Wellcome Trust FutureScope grant (104111/Z/14/Z Wellcome Centre for Integrative Parasitology to JFQ). SBC is supported by a grant from the Annie McNab Bequest (CRUK Beatson Institute), Breast Cancer Now (2018JulPR1101, 2019DecPhD1349, 2019DecPR1424), Cancer Research Institute (CLIP award), Cancer Research UK (RCCCEA-Nov21\100003, EDDPGM-Nov21\100001, DRCNPG-Jun22\100007), and Pancreatic Cancer Research and Worldwide Cancer Research (22-0135). NAM is supported by a BBSRC Institute Strategic Programme (BBS/E/D/20002173 and BB/X010937/1). -/-
Funding Information:
We thank Julie Galbraith and Pawel Herzyk (Glasgow Polyomics, University of Glasgow) for their support with library preparation and sequencing. Similarly, we would like to thank the technical staff at the University of Glasgow Biological Services for their assistance in maintaining optimal husbandry conditions and comfort for the animals used in this study. We would also like to thank Frazer Bell, Lynn Stevenson, and the rest of the University of Glasgow Veterinary school histopathology service for the technical assistance with histological advice and preparations. We thank the Maria Kasper Lab (Karolinska Institutet, Sweden) for their advice on single cell skin dissociation, and Rebecca O’Brien (National Jewish Health, USA) for providing the Vγ4/6-/-mice. We also thank Shinya Hatano and Yasunobu Yoshikai (Kyushu University, Fukuoka, Japan) for providing the Vγ6 antibody. We thank Dr Jean Rodgers for the work conducted under her Home Office Animal License (PPL No. PC8C3B25C). This work was funded by a Sir Henry Wellcome postdoctoral fellowship (221640/Z/20/Z to JFQ), a Wellcome Trust FutureScope grant (104111/Z/14/Z Wellcome Centre for Integrative Parasitology to JFQ), a University of Glasgow Lord Kelvin Adam Smith Leadership Fellowship (to JFQ), and a Wellcome Trust Senior Research fellow (209511/Z/17/Z to AML). RH is a Wellcome Trust PhD student (Wellcome Trust 218518/Z/19/Z). MCS, PC, JO, AC, and NRK are supported by a Wellcome Trust Senior Research fellowship (209511/Z/17/Z) awarded to AML. JO is also supported by a Wellcome Trust FutureScope grant (104111/Z/14/Z Wellcome Centre for Integrative Parasitology to JFQ). SBC is supported by a grant from the Annie McNab Bequest (CRUK Beatson Institute), Breast Cancer Now (2018JulPR1101, 2019DecPhD1349, 2019DecPR1424), Cancer Research Institute (CLIP award), Cancer Research UK (RCCCEA-Nov21\100003, EDDPGM-Nov21\100001, DRCNPG-Jun22\100007), and Pancreatic Cancer Research and Worldwide Cancer Research (22-0135). NAM is supported by a BBSRC Institute Strategic Programme (BBS/E/D/20002173 and BB/X010937/1).
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/8/29
Y1 - 2023/8/29
N2 - African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6
+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6
+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6
+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.
AB - African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6
+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6
+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6
+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.
KW - African trypanosomes
KW - γδ T cells
KW - Vγ6+ 23 cells
KW - adipocytes skin inflammation.skin inflammation.
KW - skin inflammation
U2 - 10.1038/s41467-023-40962-y
DO - 10.1038/s41467-023-40962-y
M3 - Article
C2 - 37644007
SN - 2041-1723
VL - 14
SP - 1
EP - 17
JO - Nature Communications
JF - Nature Communications
IS - 29
M1 - 5279
ER -