Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions

Asbjørn Christophersen; Eivind G Lund; Omri Snir; Elsa Solà; Chakravarthi Kanduri; Shiva Dahal-Koirala; Stephanie Zühlke; Øyvind Molberg; Paul J Utz; Mina Rohani-Pichavant; Julia F Simard; Cornelia L Dekker; Knut E A Lundin; Ludvig M Sollid; Mark M Davis

doi:10.1038/s41591-019-0403-9

Distinct phenotype of CD4⁺ T cells driving celiac disease identified in multiple autoimmune conditions

Nat Med. 2019 May;25(5):734-737. doi: 10.1038/s41591-019-0403-9. Epub 2019 Mar 25.

Authors

Asbjørn Christophersen^{1

2

3

4}, Eivind G Lund^{1

2

3}, Omri Snir^{1

2

3}, Elsa Solà^{4

5}, Chakravarthi Kanduri^{1

6}, Shiva Dahal-Koirala^{1

2

3}, Stephanie Zühlke^{1

2

3}, Øyvind Molberg^{2

7}, Paul J Utz⁴, Mina Rohani-Pichavant⁴, Julia F Simard⁸, Cornelia L Dekker⁹, Knut E A Lundin^{1

2

10}, Ludvig M Sollid^{11

12

13

14}, Mark M Davis^{15

16

17}

Affiliations

¹ KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Immunology, University of Oslo, Oslo, Norway.
⁴ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Liver Unit, Hospital Clínic Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain.
⁶ Department of Informatics, University of Oslo, Oslo, Norway.
⁷ Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.
⁸ Epidemiology, Health Research and Policy, Stanford School of Medicine, Stanford, CA, USA.
⁹ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
¹¹ KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway. l.m.sollid@medisin.uio.no.
¹² Institute of Clinical Medicine, University of Oslo, Oslo, Norway. l.m.sollid@medisin.uio.no.
¹³ Department of Immunology, University of Oslo, Oslo, Norway. l.m.sollid@medisin.uio.no.
¹⁴ Department of Immunology, Oslo University Hospital, Oslo, Norway. l.m.sollid@medisin.uio.no.
¹⁵ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.
¹⁶ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.
¹⁷ The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.

Abstract

Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4⁺ T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4⁺ T cells specific for disease-driving antigens in multiple autoimmune conditions.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autoimmune Diseases / immunology*
CD4-Positive T-Lymphocytes / immunology*
Celiac Disease / classification
Celiac Disease / immunology*
Glutens / immunology
HLA-DQ Antigens / immunology
Humans
Immunophenotyping
Intestines / immunology
Lupus Erythematosus, Systemic / immunology
Scleroderma, Systemic / immunology
T-Lymphocyte Subsets / classification
T-Lymphocyte Subsets / immunology

Substances

HLA-DQ Antigens
Glutens

Abstract

Publication types

MeSH terms

Substances

Grants and funding