Professor David Withers PhD

David Withers

Institute of Immunology and Immunotherapy
Professor of Immune Regulation

Contact details

Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

David Withers is a Wellcome Trust funded Senior Research Fellow

Research in the Withers Lab is focused on understanding how memory CD4 T cell responses are generated and maintained, in particular the key cellular interactions that provide critical signals in this process. We are currently testing the role of RORgt-expressing group 3 Innate Lymphoid Cells versus other immune cell populations as checkpoints in adaptive immunity, both within secondary lymphoid tissue but also at mucosal barrier surfaces.

Qualifications

  • PhD Immunology, 2004
  • BSc (Hons) Microbiology and Virology, 2000

Biography

David Withers qualified with a BSc (Hons) in Virology and Microbiology from the University of Warwick in 2000. He went on to study for a PhD in Immunology at the Institute for Animal Health in conjunction with the University of Bristol. After obtaining his PhD, David continued his studies in the laboratory of Peter Lipsky at NIAMS, NIH, Bethseda (2004-2006). He then returned to the UK to study with Peter Lane at the University of Birmingham, cementing his interest in secondary lymphoid tissue development/structure and how this controlled CD4 T cell responses. Research in the Withers Lab is supported by the Wellcome Trust. In 2011 he was awarded a Wellcome Trust Research Career Development Fellowship to establish his own research group investigating the role of lymphoid tissue inducer cells in lymph nodes. In 2016 he was awarded a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science.

Teaching

Teaching Programmes

Postgraduate supervision

The Withers Lab currently has a full quota of PhD students and no capacity to take on more students at this time.

Research

Research themes

T cell responses, Innate Lymphoid Cells, Immunological memory.

Research activity

David's research is focused on understanding the signals involved in the development and maintenance of T cell responses, in particular, the development of memory CD4 T cells which are essential for immunological memory and thus vaccination. Understanding how memory CD4 T cells are generated and maintained is crucial for improving our ability to enhance vaccination, but also potentially to modulate unwanted self-reactivity. Much of our initial work has concentrated on cellular interactions within secondary lymphoid tissue, particularly with regard to the role of ROR t-dependent group 3 Innate Lymphoid Cells (ILC3s) in regulating CD4 T cell responses. As the lab has developed, our research has now broadened to assess epigenetic changes in T cells and ILCs, mucosal tissues as sites of effector T cell responses and models enabling in vivo assessment of immune cell migration. Most recently, we developed novel approaches to track immune cell migration into and out of tumours, establishing innovative new models that can reveal fundamental information regarding anti-tumour immunity. Research in my lab is currently focused in four complimentary areas:

  1. Dissecting the roles of ILC3s in controlling T cell responses.
  2. Analysis of memory Th1 and Th17 responses.
  3. Understanding the role of key transcription factors in dictating ILC and T cell function and fate.
  4. Analysis of immune cell recruitment and retention in tumours in vivo.

Publications

Recent publications

Article

Quraishi, MN, Acharjee, A, Beggs, AD, Horniblow, R, Tselepis, C, Gkoutos, G, Ghosh, S, Rossiter, A, Loman, N, van Schaik, W, Withers, D, Walters, JRF, Hirschfield, GM & Iqbal, TH 2020, 'A pilot integrative analysis of colonic gene expression, gut microbiota and immune infiltration in primary sclerosing cholangitis-inflammatory bowel disease: association of disease with bile acid pathways', Journal of Crohn's & Colitis. https://doi.org/10.1093/ecco-jcc/jjaa021

Perez-Toledo, M, Beristain Covarrubias, N, Channell, W, Hitchcock, J, Jones, C, Coughlan, R, Bobat, S, Jones, N, Nakamura, K, Ross, E, Rossiter, A, Rooke, J, Garcia-Gimenez, A, Jossi, S, Persaud, R, Marcial-Juarez, E, Flores-Langarica, A, Henderson, I, Withers, D, Watson, S & Cunningham, A 2020, 'Mice Deficient in T-bet Form Inducible NO Synthase–Positive Granulomas That Fail to Constrain Salmonella', Journal of Immunology, vol. 205, no. 2. https://doi.org/10.4049/jimmunol.2000089

Melo-Gonzalez, F, Kammoun, H, Evren, E, Dutton, EE, Papadopoulou, M, Bradford, BM, Tanes, C, Fardus-Reid, F, Swann, JR, Bittinger, K, Mabbott, NA, Vallance, BA, Willinger, T, Withers, DR & Hepworth, MR 2019, 'Antigen-presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria', The Journal of Experimental Medicine, vol. 216, no. 4, pp. 728-742. https://doi.org/10.1084/jem.20180871

Dutton, EE, Gajdasik, DW, Willis, C, Fiancette, R, Bishop, EL, Camelo, A, Sleeman, MA, Coccia, M, Didierlaurent, AM, Tomura, M, Pilataxi, F, Morehouse, CA, Carlesso, G & Withers, DR 2019, 'Peripheral lymph nodes contain migratory and resident innate lymphoid cell populations', Science Immunology, vol. 4, no. 35, eaau8082. https://doi.org/10.1126/sciimmunol.aau8082

Chu, C, Moriyama, S, Li, Z, Zhou, L, Flamar, A-L, Klose, CSN, Moeller, JB, Putzel, GG, Withers, DR, Sonnenberg, GF & Artis, D 2018, 'Anti-microbial Functions of group 3 innate lymphoid cells in gut-associated lymphoid tissues are regulated by G-protein-coupled receptor 183', Cell Reports, vol. 23, no. 13, pp. 3750-3758. https://doi.org/10.1016/j.celrep.2018.05.099

Flores-Langarica, A, Müller Luda, K, Persson, EK, Cook, CN, Bobat, S, Marshall, JL, Dahlgren, MW, Hägerbrand, K, Toellner, KM, Goodall, MD, Withers, D, Henderson, IR, Johansson Lindbom, B, Agace, WW & Cunningham, A 2018, 'CD103+CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin', Mucosal immunology, vol. 11, no. 3, pp. 681-692. https://doi.org/10.1038/mi.2017.105

Jones, R, Cosway, E, Willis, C, White, A, Jenkinson, W, Fehling, HJ, Anderson, G & Withers, D 2018, 'Dynamic changes in intrathymic ILC populations during murine neonatal development', European Journal of Immunology, vol. 48, no. 9, pp. 1481-1491. https://doi.org/10.1002/eji.201847511

Halim, TYF, Rana, BMJ, Walker, JA, Kerscher, B, Knolle, MD, Jolin, HE, Serrao, EM, Haim-Vilmovsky, L, Teichmann, SA, Rodewald, H-R, Botto, M, Vyse, TJ, Fallon, PG, Li, Z, Withers, DR & McKenzie, ANJ 2018, 'Tissue-restricted adaptive type 2 immunity is orchestrated by expression of the costimulatory molecule OX40L on group 2 innate lymphoid cells', Immunity, vol. 48, no. 6, pp. 1195-1207.e6. https://doi.org/10.1016/j.immuni.2018.05.003

Sevastsyanovich, YR, Withers, DR, Marriott, CL, Morris, FC, Wells, TJ, Browning, DF, Beriotto, I, Ross, E, Ali, HO, Wardius, CA, Cunningham, AF, Henderson, IR & Rossiter, AE 2017, 'Antigen localization influences the magnitude and kinetics of the endogenous adaptive immune response to recombinant Salmonella vaccines', Infection and Immunity, vol. 85, e00593-17. https://doi.org/10.1128/IAI.00593-17

Nawaf, MG, Ulvmar, MH, Withers, DR, McConnell, FM, Gaspal, FM, Webb, GJ, Jones, ND, Yagita, H, Allison, JP & Lane, PJL 2017, 'Concurrent OX40 and CD30 ligand blockade abrogates the CD4-driven autoimmunity associated with CTLA4 and PD1 blockade while preserving excellent anti-CD8 tumor immunity', Journal of Immunology, vol. 199, no. 3, pp. 974-981. https://doi.org/10.4049/jimmunol.1700088

Marriott, CL, Dutton, EE, Tomura, M & Withers, DR 2017, 'Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations', European Journal of Immunology, vol. 47, no. 5, pp. 860–871. https://doi.org/10.1002/eji.201646681

Jeffery, HC, van Wilgenburg, B, Kurioka, A, Parekh, K, Stirling, K, Roberts, S, Dutton, EE, Hunter, S, Geh, D, Braitch, MK, Rajanayagam, J, Iqbal, T, Pinkney, T, Brown, R, Withers, DR, Adams, DH, Klenerman, P & Oo, Y 2016, 'Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1', Journal of Hepatology, vol. 64, no. 5, pp. 1118–1127. https://doi.org/10.1016/j.jhep.2015.12.017

Withers, DR 2016, 'Innate lymphoid cell regulation of adaptive immunity', Immunology, vol. 149, no. 2, pp. 123-130. https://doi.org/10.1111/imm.12639

Review article

Withers, DR & Hepworth, MR 2017, 'Group 3 innate lymphoid cells: communications hubs of the intestinal immune system', Frontiers in immunology, vol. 8, 1298. https://doi.org/10.3389/fimmu.2017.01298

Bevington, SL, Cauchy, P, Withers, DR, Lane, PJL & Cockerill, PN 2017, 'T cell receptor and cytokine signaling can function at different stages to establish and maintain transcriptional memory and enable T helper cell differentiation', Frontiers in immunology, vol. 8, 204. https://doi.org/10.3389/fimmu.2017.00204

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