Preclinical study demonstrates that ITK deficiency protects against pulmonary hemorrhage in mice, indicating therapeutic potential for ITK inhibition in autoimmune lung disease.
Key Points
To evaluate the role of interleukin-2-inducible T cell kinase (ITK) in regulating the balance between destructive inflammation and tissue-protective immunity in autoimmune lung injury.
Assessed pristine-induced pulmonary hemorrhage and multi-organ injury in wild-type and ITK-deficient mice.
Performed adoptive transfer of ITK-deficient Foxp3⁺ regulatory T cells into wild-type recipient mice.
Conducted transcriptomic profiling to analyze metabolic and functional pathway alterations in ITK-deficient regulatory T cells.
ITK deficiency provided near-complete protection against pristane-induced pulmonary hemorrhage and associated multi-organ damage.
Loss of ITK expanded CD44⁺CD122⁺Eomes⁺T-bet⁺ memory-like T cells and Foxp3⁺ regulatory T cells; adoptive transfer of these regulatory T cells rescued established hemorrhage, suppressed proinflammatory cytokines, and reversed proteinuria.
Transcriptomic profiling showed ITK-deficient regulatory T cells were reprogrammed toward enhanced oxidative phosphorylation (OXPHOS), mTORC1, and STAT5 signaling programs.