The Tec kinase ITK is essential for ILC2 survival and epithelial integrity in the intestine

Hyoung-Soo Cho,Jason A Hall,Leslie J Berg,Andrea Reboldi

doi:10.1038/s41467-019-08699-9

Hyoung-Soo Cho, Jason A Hall + Show 2 more

Open Access

https://doi.org/10.1038/s41467-019-08699-9

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Abstract

Innate lymphoid cells (ILC) are lymphocytes that lack an antigen-specific receptor and are preferentially localized in non-lymphoid tissues, such as mucosal barriers. In these locations ILC respond to tissue perturbations by producing factors that promote tissue repair and improve barrier integrity. We show that mice lacking the Tec kinase ITK have impaired intestinal tissue integrity, and a reduced ability to restore homeostasis after tissue damage. This defect is associated with a substantial loss of Type 2 ILC (ILC2) in the intestinal lamina propria. Adoptive transfer of bone marrow ILC2 precursors confirms a cell-intrinsic role for ITK. Intestinal ILC2 numbers in Itk-/- mice are restored by the administration of IL-2 complexes, also leading to improved intestinal tissue damage repair. Reduced Bcl-2 expression in intestinal Itk-/- ILC2 is also restored to WT levels after IL-2 complex treatment, indicating a tissue-specific role for ITK in ILC2 survival in the intestine.

Highlights

Innate lymphoid cells (ILC) are lymphocytes that lack an antigen-specific receptor and are preferentially localized in non-lymphoid tissues, such as mucosal barriers
ILC2, at levels comparable with those seen in T cells; high expression of Itk was not shared with gut ILC1 or ILC3
ILC2 deficit was restricted to the intestinal tissues, as bone marrow (BM), lung, and mesenteric lymph nodes of Itk−/− mice showed no reduction in ILC2 proportions compared with controls (Fig. 1f, g)

Summary

Introduction

Innate lymphoid cells (ILC) are lymphocytes that lack an antigen-specific receptor and are preferentially localized in non-lymphoid tissues, such as mucosal barriers. ILC2 numbers seen in the intestinal tissue of Itk−/− mice (Fig. 1a–c). To investigate further a potential role for ITK in gut-homing receptor expression on ILC2, we assessed CCR9 and integrin α4β7 levels on ILC2 in the small and large intestinal LP from naïve WT and Itk−/− mice.

Results

Conclusion