Alain Fischer, Eric Vivier and colleagues studied a small cohort of patients with severe combined immunodeficiency (SCID) caused by mutation of the common cytokine receptor γ-chain (IL2RG) or Janus kinase 3 (JAK3). IL-2Rγc and JAK3 mediate signalling downstream of interleukin-7 (IL-7) and IL-15, which are required for T cell and natural killer (NK) cell development, respectively. ILC1, ILC2 and ILC3 subsets are also dependent on IL-7, and indeed no circulating ILCs could be detected in the peripheral blood of three JAK3-deficient patients who were analysed before treatment.
The standard treatment for the life-threatening T cell deficiency of SCID is allogeneic haematopoietic stem cell transplantation (HSCT). 18 patients with IL-2Rγc deficiency (n = 12) or JAK3 deficiency (n = 6) who had undergone HSCT (without myeloablation) many years previously were analysed for immune cell reconstitution. All patients showed T cell reconstitution of donor origin, but NK cells, ILC2s and ILC3s could not be detected in peripheral blood. A small number of ILC1s were present in the blood of a few patients but as this subset has not been well defined these might not correspond to bona fide ILC1s. Similarly, no ILCs could be found in skin and gut biopsies from these patients. Thus, the lack of circulating and tissue-resident ILCs in IL-2Rγc- and JAK3-deficient patients with SCID persists after non-myeloablative HSCT.
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