Clatworthy Lab

Home of the Cambridge Tissue Immunity Laboratory

What do we do?

We use human organs and model systems, applying single cell genomic and advanced imaging technologies to investigate tissue Immunity across different organs. We are interested in how tissue environments influence resident immune cells, how these interactions change in disease and with age, and how tissue immunity is linked across organs. Our ultimate aim is to find new and better ways of diagnosing, monitoring and treating human diseases.

Research

Kidney – We are decoding the development, function and interactions of immune cells in the human kidney in health, disease and ageing. We have a particular interest in how tissue immune cells work with epithelial cells to defend the kidney from infection but play pathogenic roles in autoimmune diseases like lupus nephritis or ANCA vasculitis and in kidney allograft rejection.
Bladder – We are investigating how immune-epithelial-fibroblast cell circuits work during homeostasis and in bladder infection, how this differs between men and women and changes with age.
CNS Border immunity – the organs of the central nervous system ((CNS), brain and spinal cord) are protected by the meninges and skull/vertebrae. We are investigating how immune cells in these border tissues protect the CNS from infection, contribute to CNS diseases (including depression/anxiety and neurodegeneration) and may be influenced by peripheral immune stimuli like gut inflammation or kidney infection.
Humoral immunity across tissues/organs – We are analysing B cells and plasma cells (cells responsible for antibody production) within different organs, investigating their potential roles beyond antibody production.
Immune responses in COVID-19 – We are studying immune cells in peripheral blood, adenoid and lung tissues to understand how the immune system responds to SARS-CoV2 and how this might contribute to pathology or might be harnessed in vaccine efforts.

We are committed to sharing our know-how and datasets, check out:

www.kidneycellatlas.org
www.CNSbordercellatlas.org
Dandelion BCR/TCR analysis - https://www.youtube.com/watch?v=pxz31b1iIFY

Publications

Key publications:

Madissoon E, Oliver AJ, Kleshchevnikov V, Wilbrey-Clark A, Polanski K, Richoz N, Ribeiro Orsi A, Mamanova L, Bolt L, Elmentaite R, Pett JP, Huang N, Xu C, He P, Dabrowska M, Pritchard S, Tuck L, Prigmore E, Perera S, Knights A, Oszlanczi A, Hunter A, Vieira SF, Patel M, Lindeboom RGH, Campos LS, Matsuo K, Nakayama T, Yoshida M, Worlock KB, Nikolić MZ, Georgakopoulos N, Mahbubani KT, Saeb-Parsy K, Bayraktar OA, Clatworthy MR, Stegle O, Kumasaka N, Teichmann SA, Meyer KB. A spatially resolved atlas of the human lung characterizes a gland-associated immune niche. Nat Genet. 2023;55(1):66-77.
Suo C, Polanski K, Dann E, Lindeboom RGH, Vilarrasa-Blasi R, Vento-Tormo R, Haniffa M, Meyer KB, Dratva LM, Tuong ZK*, Clatworthy MR*, Teichmann SA*. Dandelion uses the single-cell adaptive immune receptor repertoire to explore lymphocyte developmental origins. Nat Biotechnol. 2023 Apr 13. Co-corresponding.
Inaba A, Tuong ZK, Zhao TX, Stewart AP, Mathews R, Truman L, Sriranjan R, Kennet J, Saeb-Parsy K, Wicker L, Waldron-Lynch F, Cheriyan J, Todd JA, Mallat Z, Clatworthy MR. Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells. Nat Commun. 2023 Apr 12;14(1):2071
Guo SA, Bowyer GS, Ferdinand JR, Maes M, Tuong ZK, Gillman E, Liao M, Lindeboom RGH, Yoshida M, Worlock K, Gopee H, Stephenson E, Gao CA, Lyons PA, Smith KGC, Haniffa M, Meyer KB, Nikolić MZ, Zhang Z, Wunderink RG, Misharin AV, Dougan G, Navapurkar V, Teichmann SA*, Conway Morris A*, Clatworthy MR*. Obesity Is Associated with Attenuated Tissue Immunity in COVID-19. Am J Respir Crit Care Med. 2023;207(5):566-576.
Stewart BJ, Fergie M, Young MD, Jones C, Sachdeva A, Blain A, Bacon CM, Rand V, Ferdinand JR, James KR, Mahbubani KT, Hook L, Jonas N, Coleman N, Saeb-Parsy K, Collin M, Clatworthy MR, Behjati S, Carey CD. Spatial and molecular profiling of the mononuclear phagocyte network in classic Hodgkin lymphoma. Blood. 2023;141(19):2343-2358.

Other publications:

Fitzpatrick Z, Frazer G, Ferro A, Clare S, Bouladoux N, Ferdinand JR, Tuong ZW, Negro-Demontel ML, Suchanek O, Tajsic T, Harcourt K, Scott K, Bashford-Rogers R, Helmy A, Reich DS, Belkaid Y,Lawley T, McGavern DB^†, Clatworthy MR^†. Gut-educated IgA plasma cells defend meningeal venous sinuses. Nature. 2020; Nov;587(7834):472-476. ^†co-corresponding.
Stewart BS*, Ferdinand JR*, Young MD, Mitchell TJ, Loudon KW, Riding AM, Richoz N, Frazer GL, Staniforth JU, Vieira Braga FA, Botting R, Popescu DM, Vento-Tormo R, Stephenson E, Cagan A, Farndon SJ, Polanski K, Efremova M, Green K, Velasco-Herrera M, Guzzo C, CollorD G, Mamanova L, Aho T, Armitage JN, Riddick AC, Mushtaq I, Farrell S, Rampling D, Nicholson J, Filby A, Burge J, LisgoS, Lindsay S, Bajenoff M, Warren AY, Stewart GD, SebireN, Coleman N, Haniffa M*, Teichmann SA*, Behjati S*, Clatworthy MR*. Spatio-temporal immune zonation of the human kidney. Science 2019;365(6460):1461-1466.
Castro-DopicoT, DennisonTW, FerdinandJR, MathewsRJ, Fleming A, CliftD, StewartBJ, JingC, StrongiliK, LabzinLI, MonkEJM, Saeb-ParsyK, BryantCE, ClareS, ParkesM, ClatworthyMR. Anti-commensal IgG drives intestinal inflammation and type 17 immunity. Immunity 2019;50(4):1099-1114.