ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation

• Published in: Communications biology 2022-02, Vol.5 (1), p.162-162, Article 162
• Main Authors: Elmore, Jessica, Carter, Chavez, Redko, Amie, Koylass, Nicholas, Bennett, Amelia, Mead, Max, Ocasio-Rivera, Marinel, Huang, Weishan, Singh, Ankur, August, Avery
• Format: Article
• Language: English
• Subjects: 13/31; 38/91; 631/250; 631/250/1619/554; 64/60; Alveolitis; Alveolitis, Extrinsic Allergic - enzymology; Alveolitis, Extrinsic Allergic - immunology; Alveolitis, Extrinsic Allergic - metabolism; Biology; Biomedical and Life Sciences; CD4 antigen; Cell activation; Cell differentiation; Cytokines - metabolism; Helper cells; Humans; Hypersensitivity; Inflammation; Inflammation - metabolism; Inflammatory diseases; Interleukin 1; Interleukin 17; Itk protein; Leukocytes (neutrophilic); Life Sciences; Lymphocytes; Lymphocytes T; Pneumonia - chemically induced; Pneumonia - enzymology; Pneumonia - immunology; Pneumonia - metabolism; Pneumonitis; Protein-Tyrosine Kinases - immunology; Saccharopolyspora; T cell receptors; Th17 Cells - enzymology; Th17 Cells - immunology; Th17 Cells - metabolism; Transcriptomics
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03109-1

T helper 17 (Th17) cells develop in response to T cell receptor signals (TCR) in the presence of specific environments, and produce the inflammatory cytokine IL17A. These cells have been implicated in a number of inflammatory diseases and represent a potential target for ameliorating such diseases. The kinase ITK, a critical regulator of TCR signals, has been shown to be required for the development of Th17 cells. However, we show here that lung inflammation induced by Saccharopolyspora rectivirgula (SR) induced Hypersensitivity pneumonitis (SR-HP) results in a neutrophil independent, and ITK independent Th17 responses, although ITK signals are required for γδ T cell production of IL17A. Transcriptomic analysis of resultant ITK independent Th17 cells suggest that the SR-HP-induced extrinsic inflammatory signals may override intrinsic T cell signals downstream of ITK to rescue Th17 responses in the absence of ITK. These findings suggest that the ability to pharmaceutically target ITK to suppress Th17 responses may be dependent on the type of inflammation. The kinase Itk is normally required for differentiation of IL-17-producing CD4 T-helper (Th)17 cells however, Elmore, Carter et al. now report that Itk can be bypassed during Th17 differentiation in Saccharopolyspora rectivirgula induced hypersensitivity pneumonitis. This study suggests that some inflammatory signals can override normal T cell activation and differentiation pathways.