Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
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ABSTRACT:
SUBMITTER: Levy R
PROVIDER: S-EPMC9754768 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
Lévy Romain R Gothe Florian F Momenilandi Mana M Magg Thomas T Materna Marie M Peters Philipp P Raedler Johannes J Philippot Quentin Q Rack-Hoch Anita Lena AL Langlais David D Bourgey Mathieu M Lanz Anna-Lisa AL Ogishi Masato M Rosain Jérémie J Martin Emmanuel E Latour Sylvain S Vladikine Natasha N Distefano Marco M Khan Taushif T Rapaport Franck F Schulz Marian S MS Holzer Ursula U Fasth Anders A Sogkas Georgios G Speckmann Carsten C Troilo Arianna A Bigley Venetia V Roppelt Anna A Dinur-Schejter Yael Y Toker Ori O Bronken Martinsen Karen Helene KH Sherkat Roya R Somekh Ido I Somech Raz R Shouval Dror S DS Kühl Jörn-Sven JS Ip Winnie W McDermott Elizabeth M EM Cliffe Lucy L Ozen Ahmet A Baris Safa S Rangarajan Hemalatha G HG Jouanguy Emmanuelle E Puel Anne A Bustamante Jacinta J Alyanakian Marie-Alexandra MA Fusaro Mathieu M Wang Yi Y Kong Xiao-Fei XF Cobat Aurélie A Boutboul David D Castelle Martin M Aguilar Claire C Hermine Olivier O Cheminant Morgane M Suarez Felipe F Yildiran Alisan A Bousfiha Aziz A Al-Mousa Hamoud H Alsohime Fahad F Cagdas Deniz D Abraham Roshini S RS Knutsen Alan P AP Fevang Borre B Bhattad Sagar S Kiykim Ayca A Erman Baran B Arikoglu Tugba T Unal Ekrem E Kumar Ashish A Geier Christoph B CB Baumann Ulrich U Neven Bénédicte B Rohlfs Meino M Walz Christoph C Abel Laurent L Malissen Bernard B Marr Nico N Klein Christoph C Casanova Jean-Laurent JL Hauck Fabian F Béziat Vivien V
The Journal of experimental medicine 20221214 2
Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and ...[more]
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