Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1403155

Protein kinase D1 in myeloid lineage cells contributes to the accumulation of CXCR3 + CCR6 + nonconventional Th1 cells in the lungs and potentiates hypersensitivity pneumonitis caused by S. rectivirgula

Provisionally accepted
John D. Snyder John D. Snyder 1Taewon Yoon Taewon Yoon 1Sangmin Lee Sangmin Lee 1Priyanka Halder Priyanka Halder 2Elizabeth A. Fitzpatrick Elizabeth A. Fitzpatrick 1Ae-Kyung Yi Ae-Kyung Yi 1*
  • 1 University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, United States
  • 2 Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, United States

The final, formatted version of the article will be published soon.

    Hypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the S. rectivirgula-induced HP. Compared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to S. rectivirgula for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to S. rectivirgula. Moreover, accumulation of CXCR3 + CCR6 + nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to S. rectivirgula. Our results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to S. rectivirgula by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs.

    Keywords: Protein kinase D1, cytokines/chemokines, Inflammation, Alveolitis, Saccharopolyspora rectivirgula, Hypersensitivity pneumonitis

    Received: 18 Mar 2024; Accepted: 18 Sep 2024.

    Copyright: © 2024 Snyder, Yoon, Lee, Halder, Fitzpatrick and Yi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ae-Kyung Yi, University of Tennessee Health Science Center (UTHSC), Memphis, 38163-0002, Tennessee, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.