Gliadin-reactive vitamin D-sensitive proinflammatory ILCPs are enriched in celiac patients
Giuseppe Ercolano,
Alex Moretti,
Maryline Falquet,
Tania Wyss,
Ngoc Lan Tran,
Isis Senoner,
Maddalena Marinoni,
Massimo Agosti,
Silvia Salvatore,
Camilla Jandus,
Sara Trabanelli
Affiliations
Giuseppe Ercolano
Departement of Oncology, UNIL-CHUV, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland
Alex Moretti
Pediatric Department, Hospital “F. Del Ponte,” University of Insubria, 21100 Varese, Italy
Maryline Falquet
Departement of Oncology, UNIL-CHUV, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland
Tania Wyss
Departement of Oncology, UNIL-CHUV, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland
Ngoc Lan Tran
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland
Isis Senoner
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland
Maddalena Marinoni
Pediatric Department, Hospital “F. Del Ponte,” University of Insubria, 21100 Varese, Italy; Pediatric Onco-haematological Day Hospital, Hospital “F. Del Ponte”, ASST-Settelaghi, 21100 Varese, Italy
Massimo Agosti
Pediatric Department, Hospital “F. Del Ponte,” University of Insubria, 21100 Varese, Italy
Silvia Salvatore
Pediatric Department, Hospital “F. Del Ponte,” University of Insubria, 21100 Varese, Italy
Camilla Jandus
Departement of Oncology, UNIL-CHUV, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland
Sara Trabanelli
Departement of Oncology, UNIL-CHUV, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; Corresponding author
Summary: Celiac disease (CD) is a multisystem disease in which different organs may be affected. We investigate whether circulating innate lymphoid cells (ILCs) contribute to the CD peripheral inflammatory status. We find that the CD cytokine profile is characterized by high concentrations of IL-12p40, IL-18, and IFN-γ, paralleled by an expansion of ILC precursors (ILCPs). In the presence of the gliadin peptides p31–43 and pα-9, ILCPs from CD patients increase transglutaminase 2 (TG2) expression, produce IL-18 and IFN-γ, and stimulate CD4+ T lymphocytes. IFN-γ is also produced upon stimulation with IL-12p40 and IL-18 and is inhibited by the addition of vitamin D. Low levels of blood vitamin D correlate with high IFN-γ and ILCP presence and mark the CD population mostly affected by extraintestinal symptoms. Dietary vitamin D supplementation appears to be an interesting therapeutic approach to dampen ILCP-mediated IFN-γ production.
