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Dr Menna Clatworthy

Dr Menna  Clatworthy

University Lecturer in Transplantation Medicine

Menna Clatworthy is accepting applications for PhD students.


Research Interests

Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated via Fcgamma receptors (FcγRs), which bind to the Fc portion of IgG. They are found on most cells of the immune system including dendritic cells (DCs), macrophages, NK cells, neutrophils and B cells. FcγRs may be activating (in humans FcγRI, IIA, IIC, IIIA, and IIIB) or inhibitory (FcγRIIB). Deficiency or dysfunction of the inhibitory receptor FcyRIIB is associated with the development of autoimmune disease.

Previously we have investigated the role of FcγRIIB in regulating the immune response to pathogens, (particularly Streptococcus pneumoniae and malaria), and in conferring susceptibility to the autoimmune disease systemic lupus erythematosus.

On-going areas of research aim to increase our understanding of the breadth of antibody effector function, particularly on the dynamic behaviour of immune cells. These include:

  • FcγRs and DC trafficking
  • FcγRs in lymphangiogenesis.
  • Interactions between FcγRs and innate immune signalling pathways, including the response to tissue damage (sterile inflammation).
  • FcγRIIB and B-T interaction
  • Renal mononuclear phagocytes – including the utilisation of two-photon microscopy for dynamic imaging of immune cells within the kidney.
  • Imaging immune activation in sterile inflammation in acute tubular necrosis in the clinic (Translational).
  • The role of B cell and antibody in renal transplantation (Clinical).

 

Group members

Miriam Berry

Rebeccah Mathews

Dr Gemma Banham

    Keywords

    two-photon microscopy ; autoimmunity ; B cells ; Fc receptors ; sterile inflammation ; inflammasome ; FCgammaRIIb ; cell culture ; chemotaxis ; fluorescence microscopy ; confocal microscopy ; FACS ; dendritic cells ; lymphangiogenesis ; antibody effector function

    Topics

    • systemic lupus erythematosus
    • autoimmunity
    • acute tubular necrosis
    • transplantation
    • sterile inflammation

    Key Publications

    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, Lisgo S, Lindsay S, Bajenoff M, Warren AY, Stewart GD, Sebire N, 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-Dopico T, Dennison TW, Ferdinand JR, Mathews RJ, Fleming A, Clift D, Stewart BJ, Jing C, Strongili K, Labzin LI, Monk EJM, Saeb-Parsy K, Bryant CE, Clare S, Parkes M, Clatworthy MR. Anti-commensal IgG drives intestinal inflammation and type 17 immunity. Immunity 2019. ;50(4):1099-1114.

     

    Young MD, Mitchell TJ, Vieira Braga FA, Tran MGB, Stewart BJ, Ferdinand JR, Collord G, Botting RA, Popescu DM, Loudon KW, Vento-Tormo R, Stephenson E, Cagan A, Farndon SJ, Del Castillo Velasco-Herrera M, Guzzo C, Richoz N, Mamanova L, Aho T, Armitage JN, Riddick ACP, Mushtaq I, Farrell S, Rampling D, Nicholson J, Filby A, Burge J, Lisgo S, Maxwell PH, Lindsay S, Warren AY, Stewart GD, Sebire N, Coleman N, Haniffa M*, Teichmann SA*, Clatworthy MR*, Behjati S*. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. Science. 2018 Aug 10;361(6402):594-599. *Co-corresponding authors.

     

    Banham GD, Flint SM, Torpey NP, Lyons PA, Shanahan DN, Gibson A, Watson CJE, O'Sullivan AM, Chadwick JA, Foster KE, Jones RB, Devey LR, Richards A, Erwig LP, Savage CO, Smith KGC, Henderson RB, Clatworthy MR. A phase 2 Experimental Medicine Randomised Placebo Controlled Trial of Belimumab in Kidney Transplantation (BEL114424). Lancet. 2018. Jun 30;391(10140):2619-2630. PMID: 29910042

     

    Berry MR, Mathews RJ, Ferdinand JR, Jing C, Loudon KW, Wlodek E, Dennison TW, Kuper C, Neuhofer W, Clatworthy MR. Renal Sodium Gradient Orchestrates a Dynamic Antibacterial Defense Zone. Cell. 2017. 170(5):860-74.

     

    Clatworthy MR*, Petri Aronin C, Matthews RJ, Morgan NY, Smith KGC, Germain RN*. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes. Nature Medicine. 2014;20(12):1458-63 *Corresponding author

     

    Clatworthy MR*, Harford S, Matthews RJ, Smith KGC*. FcRIIb inhibits immune complex-induced VEGF-A production and intranodal lymphangiogenesis. Proc Nat Acad Sci USA. 2014; 111(50):17971-6.*Corresponding author.

     

    Clatworthy MR, Watson CJ, Plotnek G, Bardsley V, Chaudhry AN, Bradley JA, Smith KG.  B-cell-depleting induction therapy and acute cellular rejection. N Engl J Med. 2009;360(25):2683-5

     

    Floto RA*, Clatworthy MR*, Heilbronn KR, Rosner DR, MacAry PA, Rankin A, Lehner PJ, Ouwehand WH, Allen JM, Watkins NJ and Smith KGC. Loss of function of a lupus-associated FcRIIb polymorphism through exclusion from lipid rafts. Nature Medicine, 2005;11:1056-8  (*equal contribution).

     

    Clatworthy MR and Smith KGC. FcRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. J Exp Med 2004;199:1-8.

     

    Two-photon imaging of CD4 T cell (cyan) interacting with B cell (green) in the popliteal lymph node.

    Two photon imaging of dendritic cells in the kidney using CD11cEYFP mice.