• Priatel, John

    Titles

    Investigator, BC Children's Hospital
    Assistant Professor, Department of Pathology & Laboratory Medicine, Faculty of Medicine, University of British Columbia

    Degrees / Designations

    PhD

    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Phone
    604-875-2442
    Fax
    Lab Phone
    604-875-2450
    Mailing Address

    BC Children's Hospital Research Institute
    Room A4-148
    950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Research Areas
    • Autoimmunity
    • Primary Immunodeficiency Diseases
    • Immune Regulation
    • T cell function
    Summary

    T cells form an integral part of our immune system and are essential to fight off most infections. To perform these roles, T cells must be able to differentiate between a variety of different antigens (defined as molecules that elicit immune responses). Excessive T cell responses towards harmless-(eg. dietary) antigens may result in dangerous food allergies while T cell attack against self-antigens (healthy cells or tissue) may cause T cell-mediated self-destruction (autoimmune disease). Conversely, dampened T cell responses against infected or malignant cells may lead to immunodeficiency (associated with chronic or life-threatening infections) or expansion of cancerous cells (tumour growth). By adding to the knowledge of how T cells can be turned “on” or “off”, we hope to uncover new therapies for human diseases related to allergy, autoimmunity, immunodeficiency and cancer.

    Current Projects

    X-linked lymphoproliferative disease
    Epstein-Barr virus (EBV) is a γ-herpesvirus that infects more than 90% of the adult population, often resulting in subclinical or self-limiting infections. However, EBV poses serious health consequences for immunocompromised individuals, such as patients undergoing transplant or chemotherapeutic regimens, and is strongly associated with an expanding list of human cancers. To gain insight into immunity against EBV, we are studying a rare congenital immunodeficiency defined by exquisite sensitivity to EBV but not other pathogens called X-linked lymphoproliferative disease, a syndrome caused by mutations in the SH2D1A gene that encodes SLAM-associated protein (SAP). The inability of boys with XLP to control EBV infection results in fulminant, often fatal, infectious mononucleosis, massive expansions of EBV-infected B cells and malignant B cell lymphomas. To uncover how SAP loss contributes to susceptibility to EBV, we are investigating the role of SAP and SLAM receptors in the regulation of B cell-driven immune responses.

    Immunoregulation of autoreactive T cells
    A breakdown of immunological tolerance can result in autoreactive T cells causing organ-specific (eg. type 1 diabetes) or system-wide autoimmune diseases (systemic lupus erythematosus). Multiple mechanisms collaborate to maintain T cell tolerance and curtail potentially lethal consequences stemming from one's own immune system attacking normal, healthy tissues and cells. Although many autoreactive T cells are programmed to die during their development in the thymus, some escape into the periphery and are thought to be restrained by a tolerance mechanism called anergy (non-antigen responsive state). The preservation of autoreactive T cells through anergy may result in dire autoimmune consequences if their function could be reawakened. Conversely, the reinvigoration of anergized T cells could be of benefit for promoting anti-cancer immune responses. My research program utilizes both in vitro cellular immunology assays and mouse model systems to study the regulation of autoreactive T cells and delineate the roles of specific genes or signalling pathways in governing their function.

    Selected Publications

    Klein T, Fung S-Y, Renner F, Blank MA, Dufour A, Kang S, Bolger-Munro M, Scuril J, Priatel JJ, Schweigler P, Melkko S, Gold MR, Viner RI, Régnier CH, Turvey SE and Overall CM. (2015) The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signaling. Nature Communications 6, 8777. PMID: 26525107.

    Montane J, Obach M, Alvarez S, Bischoff L, Dai DL, Soukhatcheva G, Priatel JJ, Hardenberg G, Levings MK, Tan R, Orban PC and Verchere CB. (2015) CCL22 Prevents Rejection of Mouse Islet Allografts and Induces Donor-Specific Tolerance. Cell Transplantation 24, 2143-2154. PMID: 26423995

    Chung BK, Priatel JJ, Tan R. (2015) CD1d expression and invariant NKT cell responses in herpesvirus infections. Frontiers in Immunology 6, 312. eCollection 2015. PMID: 26161082

    van Luijn MM, Kreft KL, Jongsma ML, Mes SW, Wierenga-Wolf AF, van Meurs M, Melief MJ, van der Kant R, Janssen L, Janssen H, Tan R, Priatel JJ, Neefjes J, Laman JD and Hintzen RQ. (2015) Multiple Sclerosis-Associated CLEC16A Controls HLA Class II Expression via Late Endosome Biogenesis. Brain 138, 1531-1547. PMID: 25823473.

    Huang YH, Tsai K, Ma C, Vallance BA, Priatel JJ ** and Tan R**. (2014) SLAM-SAP Signaling Promotes Differentiation of IL-17-Producing T Cells and Progression of Experimental Autoimmune Encephalomyelitis. The Journal of Immunology 193, 5841-5853. Double asterisks (**) indicate co-senior and co-corresponding authors.PMID: 25362182.  

    Priatel JJ*, Chung BK, Tsai K and Tan R*. (2014) Natural Killer T Cell Strategies to Combat Epstein-Barr Virus Infection. Oncolmmunology Apr 9;3:e28329. eCollection 2014. Asterisk (*) designates corresponding authors. PMID: 25050206

    Roberts ME, Bishop JL, Fan X, Beer JL, Kum WW, Krebs DL, Huang M, Gill N, Priatel JJ, Finlay BB and Harder KW. (2014) Lyn Deficiency Leads to Increased Microbiota-Dependent Intestinal Inflammation and Susceptibility to Enteric Pathogens. The Journal of Immunology 193, 5249–5263. PMID: 25339668.

    McKinnon ML, Rozmus J, Fung SY, Hirschfeld AF, Del Bel KL, Thomas L, Marr N, Martin SD, Marwaha AK, Priatel JJ, Tan R, Senger C, Tsang A, Prendiville J, Junker AK, Seear M, Schultz KR, Sly LM, Holt RA, Patel MS, Friedman JM, and Turvey SE. (2014) Combined Immunodeficiency Associated with MALT1 Mutations. The Journal of Allergy and Clinical Immunology 133, 1458-1462. PMID: 24332264.

    Chung BK, Tsai K, Allan LL, Zheng DJ, Nie JC, Biggs CM, Kozak FK, van den Elzen P,  Priatel JJ# and Tan R#. (2013) Innate Immune Control of EBV-infected B cells by Invariant Natural Killer T Cells. Blood 122, 2600-2608.  #JJP and RT contributed equally to the work. PMID: 23974196

    Lee I-F, van den Elzen P, Tan R and Priatel JJ*. (2011) Natural Killer T Cells Are Required for CFA-mediated Protection from Autoimmune Diabetes. The Journal of Immunology 187, 2898–2904. Asterisk (*) designates corresponding author.  PMID: 21844383

    Omilusik K, Priatel JJ#, Chen X, Wang YT, Xu H, Choi KB, Gopaul R, McIntyre-Smith A, Teh HS, Tan R, Bech-Hansen NT, Waterfield D, Fedida D, Hunt SV, and Jefferies WA. (2011) The CaV1.4 Calcium Channel is a Critical Regulator of T Cell Receptor Signaling and Naïve T Cell Homeostasis. Immunity 35, 349-360. Number sign (#) designates co-first author. PMID: 21835646.  

    Qin H, Lee I-F, Panagiotopoulos C, Wang X, Chu AD, Utz PJ, Priatel JJ** and Tan R.** (2011) Natural Killer Cells from Children with Type 1 Diabetes Have Defects in NKG2D-dependent Function and Signaling. Diabetes 60, 857-866. Asterisks (**) designate co-senior authors. PMID: 21270236.

    Marwaha AK, Crome SQ, Panagiotopoulos C, Qin H, Ouyang Q, Xu L, Priatel JJ, Levings MK and Tan R. (2010) Cutting Edge: Increased IL-17 Secreting T Cells in Children with New-Onset Type 1 Diabetes. The Journal of Immunology 185, 3814–3818. PMID: 20810982.

    Priatel JJ*, Chen X, Huang Y-H, Chow MT, Zenewicz LA, Coughlin JJ, Shen H, Stone JC, Tan R, Teh HS. (2010) RasGRP1 Regulates Antigen-induced Developmental Programming by Naive CD8 T Cells. The Journal of Immunology 184, 666-676. Asterisk (*) indicates corresponding author. PMID: 20007535.

    Grants

    CIHR Operating Grant: Immune functions of CLEC16A and its roles in autoimmune diabetes (co-applicant).

    CIHR Operating Grant: Understanding the Novel Human Primary Immunodeficiency Caused by MALT1 Mutations (co-applicant).

    Honours & Awards

    Canadian Institute of Health Research Fellowship Award

    Canadian Society for Immunology Travel Award

    Mathew Babicki Award
    Research Group Members
    • Xiaoxia Wang (lab manager)
    • Huilian Qin (technician)
    • Yu-Hsuan-Huang (PhD student)
    • Kevin Tsai (PhD student)
    • Sohyeong Kang (M.Sc. student) 
    • Kevin Zou (volunteer)