doi: 10.1126/sciimmunol.adz8360.
Epub 2026 Feb 27.
Human LFA-1 governs T cell immune surveillance of the skin
Ahmad Yatim
1
2
3
, Leila Youssefian
4
, Aida Idani
5
, Haralambos Mourelatos
1
6
, Nasrin Alipour Olyaei
5
, Laleh Habibi
7
8
, Jessica N Peel
1
, Maira Gaballa
1
, Colin Kim
1
, Danyel Lee
1
2
3
, Corentin Le Floc'h
2
3
, Yi-Hao Chan
1
, Marta Martin-Fernandez
9
10
, Léo Pelletier
2
3
, Koji Nakajima
1
, Antoine Fayand
2
3
, Mana Momenilandi
2
3
, Yoann Seeleuthner
2
3
, Matthieu Chaldebas
1
2
3
, Amir Hossein Saeidian
11
, Hamidreza Mahmoudi
12
, Neda Nikbakht
13
, Caroline Deswarte
2
3
, Nesrine Kerrouche
14
, Houria Sahel
15
, Nima Parvaneh
16
, Banafshe Tamizifar
17
, Roya Sherkat
18
, Johan Chanal
19
, Alireza Firooz
20
, Zahra Alizadeh
8
21
, Lazaro Lorenzo-Diaz
2
3
, Alice-Andrée Mariaggi
22
, Masato Ogishi
1
, Antoine Diep
23
, Boualem Hammadi
24
, Nacim Kerrouche
1
2
3
, Darawan Rinchai
1
, Sahar Sedighzadeh
25
, Soophia Mehrjooy
25
, Seyed Mohammad Akrami
7
25
, Cedric Lenormand
26
, Mirjana Radosavljevic
5
27
, Jérémie Rosain
1
2
3
28
, Shen-Ying Zhang
1
2
3
, Bertrand Boisson
1
2
3
, Peng Zhang
1
2
3
, Stéphanie Boisson-Dupuis
1
2
3
, James G Krueger
29
, Jean-Luc Prétet
30
, Tim Waterboer
31
, Zahra Pourpak
8
21
, Mohammad Reza Fazlollahi
8
21
, Laurent Abel
1
2
3
, Dusan Bogunovic
9
, Mohammad Shahrooei
25
, Aurélie Cobat
1
2
3
, Raphael Carapito
5
27
, Anne Molitor
5
, Hassan Vahidnezhad
32
33
34
35
, Vivien Béziat
1
2
3
, Seiamak Bahram
5
27
, Emmanuelle Jouanguy
1
2
3
, Jean-Laurent Casanova
1
2
3
36
37
Affiliations
Affiliations
- 1 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
- 2 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.
- 3 Paris Cité University, Imagine Institute, Paris, France.
- 4 Department of Pathology, Cytogenetics Laboratory, City of Hope National Medical Center, Irwindale, CA, USA.
- 5 Laboratoire d'ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut Thématique Interdisciplinaire TRANSPLANTEX NG, Université de Strasbourg, Strasbourg, France.
- 6 Weill Cornell/Rockefeller/Memorial Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.
- 7 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- 8 Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- 9 Department of Pediatrics and Center for Genetic Errors of Immunity, Columbia University Medical Center, New York, NY, USA.
- 10 Rare Diseases Research Institute (IIER), Instituto de Salud Carlos III, Madrid, Spain.
- 11 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
- 12 Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran.
- 13 Department of Dermatology and Cutaneous Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
- 14 Établissement Public de Santé de Proximité de Cheraga, Polyclinique de Cheraga, Department of Dermatology, Algiers, Algeria.
- 15 Department of Dermatology, CHU Bab El Oued, Faculty of Medicine, University of Algiers 1, Algiers, Algeria.
- 16 Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.
- 17 Dermatology Clinic, Tehran, Iran.
- 18 Immunodeficiency Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
- 19 Service de Dermatologie, Hôpital Cochin-Port Royal, Paris, France.
- 20 Center for Research and Training in Skin Disease and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
- 21 Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
- 22 Laboratory of Virology, Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Hospital, Paris, France.
- 23 Department of Immunology, Saint-Louis Hospital, Paris, France.
- 24 General Chemistry Laboratory, Department of Clinical Chemistry, APHP, Necker Hospital for Sick Children, Paris, France.
- 25 Dr. Shahrooei Lab, Tehran, Iran.
- 26 Dermatologic Clinic, University of Strasbourg, Strasbourg University Hospital, Strasbourg, France.
- 27 Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France.
- 28 Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France.
- 29 Laboratory of Investigative Dermatology, Rockefeller University, New York, NY, USA.
- 30 Université Marie et Louis Pasteur, CHU Besançon, CNRS, Chrono-environnement (UMR 6249), Besançon, France.
- 31 Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 32 Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- 33 Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- 34 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- 35 Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- 36 Department of Pediatrics, Necker Hospital for Sick Children, Paris, France.
- 37 Howard Hughes Medical Institute, New York, NY, USA.
- PMID: 41758928
- DOI: 10.1126/sciimmunol.adz8360
Item in Clipboard
Human LFA-1 governs T cell immune surveillance of the skin
Ahmad Yatim et al.
Sci Immunol.
.
Display options
Format
doi: 10.1126/sciimmunol.adz8360.
Epub 2026 Feb 27.
Authors
Ahmad Yatim
1
2
3
, Leila Youssefian
4
, Aida Idani
5
, Haralambos Mourelatos
1
6
, Nasrin Alipour Olyaei
5
, Laleh Habibi
7
8
, Jessica N Peel
1
, Maira Gaballa
1
, Colin Kim
1
, Danyel Lee
1
2
3
, Corentin Le Floc'h
2
3
, Yi-Hao Chan
1
, Marta Martin-Fernandez
9
10
, Léo Pelletier
2
3
, Koji Nakajima
1
, Antoine Fayand
2
3
, Mana Momenilandi
2
3
, Yoann Seeleuthner
2
3
, Matthieu Chaldebas
1
2
3
, Amir Hossein Saeidian
11
, Hamidreza Mahmoudi
12
, Neda Nikbakht
13
, Caroline Deswarte
2
3
, Nesrine Kerrouche
14
, Houria Sahel
15
, Nima Parvaneh
16
, Banafshe Tamizifar
17
, Roya Sherkat
18
, Johan Chanal
19
, Alireza Firooz
20
, Zahra Alizadeh
8
21
, Lazaro Lorenzo-Diaz
2
3
, Alice-Andrée Mariaggi
22
, Masato Ogishi
1
, Antoine Diep
23
, Boualem Hammadi
24
, Nacim Kerrouche
1
2
3
, Darawan Rinchai
1
, Sahar Sedighzadeh
25
, Soophia Mehrjooy
25
, Seyed Mohammad Akrami
7
25
, Cedric Lenormand
26
, Mirjana Radosavljevic
5
27
, Jérémie Rosain
1
2
3
28
, Shen-Ying Zhang
1
2
3
, Bertrand Boisson
1
2
3
, Peng Zhang
1
2
3
, Stéphanie Boisson-Dupuis
1
2
3
, James G Krueger
29
, Jean-Luc Prétet
30
, Tim Waterboer
31
, Zahra Pourpak
8
21
, Mohammad Reza Fazlollahi
8
21
, Laurent Abel
1
2
3
, Dusan Bogunovic
9
, Mohammad Shahrooei
25
, Aurélie Cobat
1
2
3
, Raphael Carapito
5
27
, Anne Molitor
5
, Hassan Vahidnezhad
32
33
34
35
, Vivien Béziat
1
2
3
, Seiamak Bahram
5
27
, Emmanuelle Jouanguy
1
2
3
, Jean-Laurent Casanova
1
2
3
36
37
Affiliations
- 1 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
- 2 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.
- 3 Paris Cité University, Imagine Institute, Paris, France.
- 4 Department of Pathology, Cytogenetics Laboratory, City of Hope National Medical Center, Irwindale, CA, USA.
- 5 Laboratoire d'ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut Thématique Interdisciplinaire TRANSPLANTEX NG, Université de Strasbourg, Strasbourg, France.
- 6 Weill Cornell/Rockefeller/Memorial Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.
- 7 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- 8 Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- 9 Department of Pediatrics and Center for Genetic Errors of Immunity, Columbia University Medical Center, New York, NY, USA.
- 10 Rare Diseases Research Institute (IIER), Instituto de Salud Carlos III, Madrid, Spain.
- 11 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
- 12 Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran.
- 13 Department of Dermatology and Cutaneous Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
- 14 Établissement Public de Santé de Proximité de Cheraga, Polyclinique de Cheraga, Department of Dermatology, Algiers, Algeria.
- 15 Department of Dermatology, CHU Bab El Oued, Faculty of Medicine, University of Algiers 1, Algiers, Algeria.
- 16 Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.
- 17 Dermatology Clinic, Tehran, Iran.
- 18 Immunodeficiency Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
- 19 Service de Dermatologie, Hôpital Cochin-Port Royal, Paris, France.
- 20 Center for Research and Training in Skin Disease and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
- 21 Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
- 22 Laboratory of Virology, Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Hospital, Paris, France.
- 23 Department of Immunology, Saint-Louis Hospital, Paris, France.
- 24 General Chemistry Laboratory, Department of Clinical Chemistry, APHP, Necker Hospital for Sick Children, Paris, France.
- 25 Dr. Shahrooei Lab, Tehran, Iran.
- 26 Dermatologic Clinic, University of Strasbourg, Strasbourg University Hospital, Strasbourg, France.
- 27 Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France.
- 28 Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France.
- 29 Laboratory of Investigative Dermatology, Rockefeller University, New York, NY, USA.
- 30 Université Marie et Louis Pasteur, CHU Besançon, CNRS, Chrono-environnement (UMR 6249), Besançon, France.
- 31 Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 32 Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- 33 Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- 34 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- 35 Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- 36 Department of Pediatrics, Necker Hospital for Sick Children, Paris, France.
- 37 Howard Hughes Medical Institute, New York, NY, USA.
- PMID: 41758928
- DOI: 10.1126/sciimmunol.adz8360
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Abstract
The human integrin lymphocyte function-associated antigen 1 (LFA-1; αLβ2) is broadly expressed on leukocytes and involved in various intercellular adhesions. We report complete LFA-1 deficiency because of inherited αL (CD11a) deficiency in otherwise healthy adults of various ancestries with skin lesions due to commensal papillomaviruses. The patients had no history of invasive infections characteristic of children with inherited deficiency of β2 (CD18), which forms heterodimers with αL, αM (CD11b), αX (CD11c), or αD (CD11d). The development and function of leukocyte subsets are largely preserved in the absence of LFA-1. However, the transendothelial migration of skin-tropic cutaneous lymphocyte antigen (CLA)+ memory T cells is severely impaired, resulting in their selective sequestration in the blood. Conversely, alternative integrins mediate the extravasation of other leukocytes, including other T cell subsets, to other tissues. Human LFA-1 is required for steady-state T cell homing to the skin and control of papillomaviruses but is otherwise largely redundant. Integrin-mediated T cell compartmentalization is thus essential for organ-selective immune surveillance.