Fibrosing interstitial lung diseases (ILDs) are a heterogeneous group of chronic, progressive and eventually lethal lung diseases with few treatment options. Despite their apparent inflammatory nature, in most cases, immunosuppressive drugs resulted useless if not harmful. Therefore, in the last decades, researches on ILDs have been mainly focused on aberrant wound healing carried out by fibroblasts/myofibroblasts and the role of transforming growth factor-ß1 (TGF-ß1)-driven remodeling, along with the interplay between fibroblasts and alveolar epithelial cells resulting in the loss of alveolar architecture and function. However, recent data suggest that both innate and adaptive immune responses are partly responsible for the triggering and maintenance of fibrogenic processes.
Several studies have demonstrated that lung M1 and M2 macrophages are involved in the pathogenesis of pulmonary fibrosis and, in particular, M2-like macrophages produce large amounts of TGF-ß1. Global impairment of T regulatory (Treg) cells was observed in Idiopathic pulmonary fibrosis (IPF) and that correlated with the disease severity. Further studies in animal models have provided contrasting results, suggesting that activated T reg cells are strong inducers of lung fibrosis through the expression of TGF-ß1, while additional data have outlined the inverse correlation between these cells and disease progression in humans. Moreover, depletion of natural killer (NK) cells along with the imbalance of the T helper 17 (Th17)/Treg axis have suggested an immune signature in IPF which shares similarities with cancer-related immune perturbations. More recently, proliferation/activation of T follicular helper cells and a decrease of B regulatory (Breg) cells have been found to occur in the peripheral blood of IPF patients suggesting that aberration of humoral immunity may also be involved in such a scenario. Furthermore, dysregulation of dendritic cells (DCs) function/maturation is also likely to have a role in fibrogenesis: immature DCs accumulate in the fibrotic lung, while mature DCs with non-proliferating B and T cells create ectopic organized lymphoid structures in the lung of IPF patients. Finally, recent evidence suggests that mucosal immunity compound (IgA, IgA producing B cells) might also trigger and/or enhance the fibrotic process.
In this Research Topic, we propose to describe recent advances on how immune and fibrotic pathways intertwine, ultimately leading to chronic lung scarring. We will also discuss how recent studies, deciphering the role of immune cells in lung fibrosis, can pave the way for innovative treatments, beyond currently available antifibrotic therapy. We welcome authors to submit Original Research, Review, Mini-Review, Case Report, and Perspective articles focusing on, but not limited to, the following topics:
1. The role of immune cells (macrophages, DCs, Treg, Breg, Th17, and NK cells) in ILDs.
2. Immune cells as potential targets for innovative treatments.
3. Mucosal immunity as a driver of fibrosis.
4. Pre-clinical models that may recapitulate immune pathways in fibrosis.
Fibrosing interstitial lung diseases (ILDs) are a heterogeneous group of chronic, progressive and eventually lethal lung diseases with few treatment options. Despite their apparent inflammatory nature, in most cases, immunosuppressive drugs resulted useless if not harmful. Therefore, in the last decades, researches on ILDs have been mainly focused on aberrant wound healing carried out by fibroblasts/myofibroblasts and the role of transforming growth factor-ß1 (TGF-ß1)-driven remodeling, along with the interplay between fibroblasts and alveolar epithelial cells resulting in the loss of alveolar architecture and function. However, recent data suggest that both innate and adaptive immune responses are partly responsible for the triggering and maintenance of fibrogenic processes.
Several studies have demonstrated that lung M1 and M2 macrophages are involved in the pathogenesis of pulmonary fibrosis and, in particular, M2-like macrophages produce large amounts of TGF-ß1. Global impairment of T regulatory (Treg) cells was observed in Idiopathic pulmonary fibrosis (IPF) and that correlated with the disease severity. Further studies in animal models have provided contrasting results, suggesting that activated T reg cells are strong inducers of lung fibrosis through the expression of TGF-ß1, while additional data have outlined the inverse correlation between these cells and disease progression in humans. Moreover, depletion of natural killer (NK) cells along with the imbalance of the T helper 17 (Th17)/Treg axis have suggested an immune signature in IPF which shares similarities with cancer-related immune perturbations. More recently, proliferation/activation of T follicular helper cells and a decrease of B regulatory (Breg) cells have been found to occur in the peripheral blood of IPF patients suggesting that aberration of humoral immunity may also be involved in such a scenario. Furthermore, dysregulation of dendritic cells (DCs) function/maturation is also likely to have a role in fibrogenesis: immature DCs accumulate in the fibrotic lung, while mature DCs with non-proliferating B and T cells create ectopic organized lymphoid structures in the lung of IPF patients. Finally, recent evidence suggests that mucosal immunity compound (IgA, IgA producing B cells) might also trigger and/or enhance the fibrotic process.
In this Research Topic, we propose to describe recent advances on how immune and fibrotic pathways intertwine, ultimately leading to chronic lung scarring. We will also discuss how recent studies, deciphering the role of immune cells in lung fibrosis, can pave the way for innovative treatments, beyond currently available antifibrotic therapy. We welcome authors to submit Original Research, Review, Mini-Review, Case Report, and Perspective articles focusing on, but not limited to, the following topics:
1. The role of immune cells (macrophages, DCs, Treg, Breg, Th17, and NK cells) in ILDs.
2. Immune cells as potential targets for innovative treatments.
3. Mucosal immunity as a driver of fibrosis.
4. Pre-clinical models that may recapitulate immune pathways in fibrosis.
