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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

    Clatworthy MR, Matthews R, Doehler B, Willcocks L, Opelz G, Smith KG. De-functioning polymorphism in the inhibitory receptor FcγRIIB does not impact upon kidney allograft survival. Clin Exp Immunol. 2014 Dec;178 Suppl 1:159-61. 

    Clatworthy MR. B cell modulation in transplantation. Clin Exp Immunol. 2014;178 Suppl 1:61-3.

    Clatworthy MR, Harford SK, Mathews RJ, Smith KG.FcγRIIb inhibits immune complex-induced VEGF-A production and intranodal lymphangiogenesis. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17971-6. d

    Clatworthy MR, Petrie Aronin CE, Matthews RJ, Morgan NY, Smith KG, Germain RN. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes. Nature Medicine (2014) doi:10.1038/nm.3709

    Clatworthy MR, Matthews RJ, Doehler B, Willcocks LC, Opelz G, Smith KG. Defunctioning Polymorphism in the Immunoglobulin G Inhibitory Receptor (FcγRIIB-T/T232) Does not Impact on Kidney Transplant or Recipient Survival. Transplantation. 2014 Aug 15;98(3):285-91.

    Subramanian N, Natarajan K, Clatworthy MR, Wang Z, Germain RN. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell 2013; 153(2):348-61

    Espeli M, Clatworthy MR, Bokers S, Lawler K, Cutler A, Kontgen F, Lyons P, Smith KGC. Analysis of a wild mouse Fcgr2b promoter variant reveals a novel role for FcγRIIb in the control of the germinal center and autoimmunity. J Exp Med. 2012;

    Clatworthy MR, Kettunen MI, Hu D, Mathews RJ, Witney TH, Gallagher F, Jarvis L, Smith KG, Brindle KM. Hyperpolarised [1,4-13C2]fumarate allows early, non-invasive diagnosis of acute tubular necrosis. Proc Nat Acad Sci USA. 2012; 109(33):13374-9.

    Smith KGC, Clatworthy MR. FcgRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat Rev Immunol. 2010;10(5):328-43.

    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.

    Clatworthy MR, Willcocks L, Urban B, Langhorne J, Williams T, Peshu N, Watkins N, Floto RA, Smith KGC. SLE-associated defects in the inhibitory receptor FcgammaRIIb reduce susceptibility to malaria. Proc Nat Acad Sci USA 2007; 104:7169–74.

    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 FcgammaRIIb polymorphism through exclusion from lipid rafts. Nature Medicine, 2005;11:1056–8

    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.