From Lysosomal Storage Diseases to NKT Cell Activation and Back

Lysosomal storage diseases (LSDs) are inherited metabolic disorders characterized by the accumulation of different types of substrates in the lysosome. With a multisystemic involvement, LSDs often present a very broad clinical spectrum. In many LSDs, alterations of the immune system were described. Special emphasis was given to Natural Killer T (NKT) cells, a population of lipid-specific T cells that is activated by lipid antigens bound to CD1d (cluster of differentiation 1 d) molecules at the surface of antigen-presenting cells. These cells have important functions in cancer, infection, and autoimmunity and were altered in a variety of LSDs’ mouse models. In some cases, the observed decrease was attributed to defects in either lipid antigen availability, trafficking, processing, or loading in CD1d. Here, we review the current knowledge about NKT cells in the context of LSDs, including the alterations detected, the proposed mechanisms to explain these defects, and the relevance of these findings for disease pathology. Furthermore, the effect of enzyme replacement therapy on NKT cells is also discussed.

[1]  C. Pereira,et al.  CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity , 2016, Journal of immunology research.

[2]  Katherine B. LeClair,et al.  iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy. , 2016, Cell metabolism.

[3]  P. Brennan,et al.  Activation strategies for invariant natural killer T cells , 2016, Immunogenetics.

[4]  P. Savage,et al.  The processing and presentation of lipids and glycolipids to the immune system , 2016, Immunological reviews.

[5]  K. Fujita,et al.  Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice , 2016, Scientific Reports.

[6]  G. De Libero,et al.  The Immunology of CD1- and MR1-Restricted T Cells. , 2016, Annual review of immunology.

[7]  L. Mori,et al.  Globotriaosylceramide inhibits iNKT‐cell activation in a CD1d‐dependent manner , 2016, European journal of immunology.

[8]  H. Veiga-Fernandes,et al.  IL-9 Expression by Invariant NKT Cells Is Not Imprinted during Thymic Development , 2015, The Journal of Immunology.

[9]  Vipin Kumar,et al.  Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer , 2015, Front. Immunol..

[10]  H. Virgin,et al.  Invariant NKT Cells Require Autophagy To Coordinate Proliferation and Survival Signals during Differentiation , 2015, The Journal of Immunology.

[11]  C. Hollak,et al.  The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease. , 2015, Best practice & research. Clinical endocrinology & metabolism.

[12]  D. Hughes,et al.  Non-neuronopathic lysosomal storage disorders: Disease spectrum and treatments. , 2015, Best practice & research. Clinical endocrinology & metabolism.

[13]  A. Ballabio,et al.  Lysosomal storage diseases: from pathophysiology to therapy. , 2015, Annual review of medicine.

[14]  G. Besra,et al.  Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue , 2014, Nature Immunology.

[15]  M. Dhodapkar,et al.  Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation. , 2015, Blood.

[16]  G. Besra,et al.  Essential role for autophagy during invariant NKT cell development , 2014, Proceedings of the National Academy of Sciences.

[17]  I. Maričić,et al.  Recognition of Lysophosphatidylcholine by Type II NKT Cells and Protection from an Inflammatory Liver Disease , 2014, The Journal of Immunology.

[18]  B. L. Anderson,et al.  The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides. , 2014, Immunity.

[19]  G. Wiederschain,et al.  Secondary biochemical and morphological consequences in lysosomal storage diseases , 2014, Biochemistry (Moscow).

[20]  Vipin Kumar,et al.  Different subsets of natural killer T cells may vary in their roles in health and disease , 2014, Immunology.

[21]  Laura Segatori.  Impairment of homeostasis in lysosomal storage disorders , 2014, IUBMB life.

[22]  Vincenzo Cerundolo,et al.  Biology of CD1- and MR1-restricted T cells. , 2014, Annual review of immunology.

[23]  P. Cresswell,et al.  Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation , 2013, Proceedings of the National Academy of Sciences.

[24]  Lunawati L. Bennett,et al.  Gaucher Disease and Its Treatment Options , 2013, The Annals of pharmacotherapy.

[25]  C. Sá-Miranda,et al.  Invariant natural killer T cells are phenotypically and functionally altered in Fabry disease. , 2013, Molecular genetics and metabolism.

[26]  Jelena S. Bezbradica,et al.  Role for lysosomal phospholipase A2 in iNKT cell-mediated CD1d recognition , 2013, Proceedings of the National Academy of Sciences.

[27]  L. Graça,et al.  Induced IL-17–Producing Invariant NKT Cells Require Activation in Presence of TGF-β and IL-1β , 2013, The Journal of Immunology.

[28]  S. Teneberg,et al.  Identification of novel glycolipid ligands activating a sulfatide‐reactive, CD1d‐restricted, type II natural killer T lymphocyte , 2012, European journal of immunology.

[29]  S. Balk,et al.  Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. , 2012, Immunity.

[30]  Anneliese O. Speak,et al.  Globosides but Not Isoglobosides Can Impact the Development of Invariant NKT Cells and Their Interaction with Dendritic Cells , 2012, The Journal of Immunology.

[31]  G. Besra,et al.  Natural killer T cells in adipose tissue prevent insulin resistance. , 2012, The Journal of clinical investigation.

[32]  S. Cardell,et al.  Immunomodulatory Type II Natural Killer T Lymphocytes in Health and Disease , 2012, Scandinavian journal of immunology.

[33]  E. Adams,et al.  The majority of CD1d‐sulfatide‐specific T cells in human blood use a semiinvariant Vδ1 TCR , 2012, European journal of immunology.

[34]  Anneliese O. Speak,et al.  Invariant natural killer T cells are not affected by lysosomal storage in patients with Niemann‐Pick disease type C , 2012, European journal of immunology.

[35]  M. S. Sá Miranda,et al.  Enzyme replacement therapy partially prevents invariant Natural Killer T cell deficiency in the Fabry disease mouse model. , 2012, Molecular genetics and metabolism.

[36]  Vrajesh V. Parekh,et al.  Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice , 2012, Proceedings of the National Academy of Sciences.

[37]  S. Sansano,et al.  Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus , 2012, Nature Immunology.

[38]  G. De Libero,et al.  Novel insights into lipid antigen presentation. , 2012, Trends in immunology.

[39]  C. Vargas,et al.  Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy. , 2012, Biochimica et biophysica acta.

[40]  Ann Atzberger,et al.  Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells , 2011, PloS one.

[41]  H. de la Salle,et al.  Fine tuning by human CD1e of lipid-specific immune responses , 2011, Proceedings of the National Academy of Sciences.

[42]  F. Choy,et al.  Gaucher Disease and Cancer: Concept and Controversy , 2011, International journal of cell biology.

[43]  L. Rogge,et al.  Proinflammatory Environment Dictates the IL-17–Producing Capacity of Human Invariant NKT Cells , 2011, The Journal of Immunology.

[44]  M. Smyth,et al.  Presumed guilty: natural killer T cell defects and human disease , 2011, Nature Reviews Immunology.

[45]  S. Kaufmann,et al.  Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells. , 2010, Immunity.

[46]  F. Platt,et al.  Common and Uncommon Pathogenic Cascades in Lysosomal Storage Diseases* , 2010, The Journal of Biological Chemistry.

[47]  I. Maričić,et al.  Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid , 2010, Proceedings of the National Academy of Sciences.

[48]  P. Popovich,et al.  Journal of Neuroinflammation Open Access Research Mucopolysaccharidosis Iiib, a Lysosomal Storage Disease, Triggers a Pathogenic Cns Autoimmune Response , 2022 .

[49]  D. Godfrey,et al.  Raising the NKT cell family , 2010, Nature Immunology.

[50]  M. Cosma,et al.  Development and maturation of invariant NKT cells in the presence of lysosomal engulfment , 2009, European journal of immunology.

[51]  E. Adams,et al.  Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes , 2009, PLoS biology.

[52]  D. Doherty,et al.  Invariant NKT cells and CD1d+ cells amass in human omentum and are depleted in patients with cancer and obesity , 2009, European journal of immunology.

[53]  C. A. Fossati,et al.  Leukocyte perturbation associated with Fabry disease , 2009, Journal of Inherited Metabolic Disease.

[54]  J. Oliveira,et al.  Anomalies in conventional T and invariant natural killer T‐cell populations in Fabry mice but not in Fabry patients , 2008, British journal of haematology.

[55]  S. Jagannath,et al.  Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer. , 2008, Blood.

[56]  Kumud Kumari,et al.  Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell‐clonotypic monoclonal antibody, 6B11 , 2007, Immunology.

[57]  F. Compostella,et al.  Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolism , 2007, European journal of immunology.

[58]  G. Besra,et al.  Distinct Endosomal Trafficking Requirements for Presentation of Autoantigens and Exogenous Lipids by Human CD1d Molecules1 , 2007, The Journal of Immunology.

[59]  P. Savage,et al.  The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells , 2007, The Journal of experimental medicine.

[60]  P. Cresswell,et al.  Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules , 2007, Proceedings of the National Academy of Sciences.

[61]  David S. Wishart,et al.  The Online Metabolic and Molecular Bases of Inherited Disease; Chapter 3.1: Metabolism and Metabolic Disease Resources on the Web, Page 1 , 2007 .

[62]  R. Dwek,et al.  Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases , 2006, The Journal of experimental medicine.

[63]  P. Savage,et al.  Cutting Edge: Impaired Glycosphingolipid Trafficking and NKT Cell Development in Mice Lacking Niemann-Pick Type C1 Protein1 , 2006, The Journal of Immunology.

[64]  J. Salamero,et al.  Assistance of Microbial Glycolipid Antigen Processing by CD1e , 2005, Science.

[65]  Fernando A. Arosa,et al.  Evidence for a link between sphingolipid metabolism and expression of CD1d and MHC‐class II: monocytes from Gaucher disease patients as a model , 2005, British journal of haematology.

[66]  D. Pellicci,et al.  Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples , 2005, European journal of immunology.

[67]  De,et al.  Tissue Fractionation Studies , 2005 .

[68]  R. Proia,et al.  Lysosomal Glycosphingolipid Recognition by NKT Cells , 2004, Science.

[69]  I. Maričić,et al.  Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide , 2004, The Journal of experimental medicine.

[70]  L. Kaer,et al.  NKT cells: what's in a name? , 2004, Nature Reviews Immunology.

[71]  P. Savage,et al.  Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins , 2004, Science.

[72]  P. Cresswell,et al.  Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to T cells , 2004, Nature Immunology.

[73]  H. Hirai,et al.  Cutting Edge: Analysis of Human Vα24+CD8+ NK T Cells Activated by α-Galactosylceramide-Pulsed Monocyte-Derived Dendritic Cells , 2002, The Journal of Immunology.

[74]  L. Teyton,et al.  Distinct Functional Lineages of Human Vα24 Natural Killer T Cells , 2002, The Journal of experimental medicine.

[75]  Takashi Yamamura,et al.  Functionally Distinct Subsets of CD1d-restricted Natural Killer T Cells Revealed by CD1d Tetramer Staining , 2002, The Journal of experimental medicine.

[76]  S. Balk,et al.  Cutting Edge: Compartmentalization of Th1-Like Noninvariant CD1d-Reactive T Cells in Hepatitis C Virus-Infected Liver , 2002, The Journal of Immunology.

[77]  P. Savage,et al.  Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail–truncated CD1d , 2002, Nature Immunology.

[78]  S. Tahir,et al.  Cutting Edge: A Major Fraction of Human Bone Marrow Lymphocytes Are Th2-Like CD1d-Reactive T Cells That Can Suppress Mixed Lymphocyte Responses1 , 2001, The Journal of Immunology.

[79]  L. Teyton,et al.  The Mouse Cd1d-Restricted Repertoire Is Dominated by a Few Autoreactive T Cell Receptor Families , 2001, The Journal of experimental medicine.

[80]  A. Kulkarni,et al.  Glycolipid antigen processing for presentation by CD1d molecules. , 2001, Science.

[81]  A. Dautry‐Varsat,et al.  Distinct Subsets of CD1d-restricted T Cells Recognize Self-antigens Loaded in Different Cellular Compartments , 1999, The Journal of experimental medicine.

[82]  C. Benoist,et al.  CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice , 1995, The Journal of experimental medicine.

[83]  C. Hollak,et al.  Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. , 1994, The Journal of clinical investigation.

[84]  R. Wattiaux,et al.  Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. , 1955, The Biochemical journal.