Evidence of innate lymphoid cell redundancy in humans

Frédéric Vély (1, 2) , Vincent Barlogis (3) , Blandine Vallentin (3) , Bénédicte Neven (4, 5, 6) , Christelle Piperoglou (1, 2) , Mikael Ebbo (1, 2, 7) , Thibaut Perchet (8, 9) , Maxime Petit (8, 9) , Nadia Yessaad (10) , Fabien Touzot (5, 11) , Julie Bruneau (5, 11) , Nicolas Zucchini (12) , Nizar Mahlaoui (4, 5) , Catherine Farnarier (7) , Gérard Michel (3) , Despina Moshous (4, 5, 6) , Arnaud Dujardin (13) , Stéphane Blanche (4, 5, 6) , Hergen Spits (14) , Jörg H W Distler (15) , Andreas Ramming (15) , Capucine Picard (4, 5, 6) , Rachel Golub (8, 9) , Alain Fischer (4, 5, 6, 16) , Eric Vivier (1, 2)

1 Laboratoire d'Immunologie [Hôpital de la Conception - APHM]
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM]
4 CEREDIH - Centre de Référence Déficits Immunitaires Héréditaires
5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
6 Service d'immuno-hématologie pédiatrique [CHU Necker]
7 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
8 Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4) - Lymphopoïèse
9 Cellule Pasteur
10 Mi-mAbs (C/O CIML)
11 CHU Necker - Enfants Malades [AP-HP]
12 BD Biosciences
13 Innate Pharma
14 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
15 Department of Internal Medicine and Institute for Clinical Immunology
16 Collège de France - Chaire Médecine expérimentale (A. Fischer)

Innate lymphoid cells (ILCs) have potent immunological functions in experimental conditions in mice, but their contributions to immunity in natural conditions in humans have remained unclear. We investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in patients with SCID who had mutation of the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ or the gene encoding the tyrosine kinase JAK3. T cell reconstitution was observed in patients with SCID after hematopoietic stem cell transplantation (HSCT), but the patients still had considerably fewer ILCs in the absence of myeloablation than did healthy control subjects, with the exception of rare cases of reconstitution of the ILC1 subset of ILCs. Notably, the ILC deficiencies observed were not associated with any particular susceptibility to disease, with follow-up extending from 7 years to 39 years after HSCT. We thus report here selective ILC deficiency in humans and show that ILCs might be dispensable in natural conditions, if T cells are present and B cell function is preserved.

Domains: Immunology

Frédéric Vély, Vincent Barlogis, Blandine Vallentin, Bénédicte Neven, Christelle Piperoglou, et al.. Evidence of innate lymphoid cell redundancy in humans. Nature Immunology, 2016, 17 (11), pp.1291 - 1299. ⟨10.1038/ni.3553⟩. ⟨pasteur-01392630⟩