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

Jessica Elmore, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Chavez Carter, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Amie Redko, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Nicholas Koylass, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Amelia Bennett, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Max Mead, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Marinel Ocasio-Rivera, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Weishan Huang, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA.
Ankur Singh, Nancy E & Peter C Meinig School of Biomedical Engineering and Department of Mechanical & Aerospace Engineering, Cornell University, Ithaca, NY, USA.
Avery August, Department of Microbiology & Immunology, Cornell Center for Immunology, Cornell Institute for Host Microbe-Interactions and Disease, Cornell University, Ithaca, NY, USA. averyaugust@cornell.edu.

Document Type

Article

Publication Date

2-24-2022

Abstract

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.

Publication Source (Journal or Book title)

Communications biology

First Page

162

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