@article{Responses:6422,
      recid = {6422},
      author = {Yoon, Young me},
      title = {Novel Immune Responses in Lung Injury and Fibrosis},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2023-06},
      abstract = {Fibrotic interstitial lung disease (ILD) is a group of  heterogeneous conditions characterizedby progressive  respiratory decline and early death. Current understanding  of the disease
mechanisms depends on etiological and  morphological classification of ILD subtypes. A
prevailing  paradigm is that immune cells play a pathogenic role in  immune-associated
ILDs, whereas their role in idiopathic  pulmonary fibrosis (IPF) is controversial.  However,
patients with fibrotic ILDs commonly have enlarged  lung-draining lymph nodes (LLN),
which correlate with  mortality. Our study revealed converging adaptive immune  landscapes
in LLNs of end-stage fibrotic ILD patients,  characterized by the enrichment of germinal
centers (GC),  antigen-stimulated T cells, and regulatory T cells with an  aberrant
phenotype. The presence of GC B cells in LLNs was  associated with worse respiratory
decline in patients. A  proteome-wide screening identified 17 novel auto-antigens  to which
circulating antibodies in ILD patients are  reactive. Autoantibody responses to ABLIM1, a
protein  highly expressed in fibrotic lungs, correlated with  frequencies of follicular helper T
cells and regulatory T  cells in patients’ LLNs. These findings suggest that  antigen-driven
immune responses could be a key  immunopathology that is common to end-stage fibrotic
ILDs,  even in IPF. Furthermore, we demonstrated that subtle  differences in the gut
microbiome compositions have a large  impact in lung injury response of mice in  specific
pathogen-free barrier facilities. Presence of  Proteobacteria, including Helilcobacter
hepaticus and  Desulfovibrio sp., in the gut was associated with increased  weight loss and
mortality during lung injury responses in  mice. These data support the gut-lung axis and
highlight  the potential benefit of specific alterations to the gut  microbiome compositions to
control lung injury outcomes.  Together, my dissertation developed a  comprehensive
understanding of the human immune responses  and the effect of the host-microbiota
interaction during  lung injury and fibrosis. This work will inform the  development of
models for mechanistic studies and patient  endotypes for effective therapeutic intervention.},
      url = {http://knowledge.uchicago.edu/record/6422},
      doi = {https://doi.org/10.6082/uchicago.6422},
}