Interpreting Immunoregulation in Lung Fibrosis: A New Branch of the Immune Model

François Huaux

doi:10.3389/fimmu.2021.690375

Abstract

Immunostimulation is recognized as an important contribution in lung fibrosis in some animal models and patient subsets. With this review, we illustrate an additional scenario covering the possible implication of immunoregulation during fibrogenesis. Available animal and human data indicate that pulmonary fibrosis also includes diverse and discrete immunoregulating populations comprising regulatory lymphocytes (T and B regs) and myeloid cells (immunosuppressive macrophages and myeloid-derived suppressive cells; MDSC). They are initially recruited to limit the establishment of deleterious inflammation but participate in the development of lung fibrosis by producing immunoregulatory mediators (mainly TGF-β1 and IL-10) that directly or indirectly stimulate fibroblasts and matrix protein deposition. The existence of this silent immunoregulatory environment sustains an alternative mechanism of fibrosis that explains why in some conditions neither pro-inflammatory cytokine deficiency nor steroid and immunosuppressive therapies limit lung fibrosis. Therefore, the persistent presence of immunoregulation is an important parameter to consider for refining therapeutical strategies in lung fibrotic disorders under non-immunostimulatory conditions.

Highlights

Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Universite Catholique de Louvain, Brussels, Belgium
Available animal and human data indicate that pulmonary fibrosis includes diverse and discrete immunoregulating populations comprising regulatory lymphocytes (T and B regs) and myeloid cells
They are initially recruited to limit the establishment of deleterious inflammation but participate in the development of lung fibrosis by producing immunoregulatory mediators that directly or indirectly stimulate fibroblasts and matrix protein deposition

Summary

Francois Huaux*

Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Universite Catholique de Louvain, Brussels, Belgium. Available animal and human data indicate that pulmonary fibrosis includes diverse and discrete immunoregulating populations comprising regulatory lymphocytes (T and B regs) and myeloid cells (immunosuppressive macrophages and myeloid-derived suppressive cells; MDSC). They are initially recruited to limit the establishment of deleterious inflammation but participate in the development of lung fibrosis by producing immunoregulatory mediators (mainly TGF-b1 and IL-10) that directly or indirectly stimulate fibroblasts and matrix protein deposition.

DIVERSE LUNG FIBROTIC DISEASES WITH DIVERSE MECHANISMS

THE RELEVANCE OF RELIABLE ANIMAL MODELS OF LUNG FIBROSIS

HISTORY OF IMMUNOREGULATING SURVEILLANCE

Regulatory T Cells

Myeloid Derived Suppressive Cells

THE DISCOVERY OF IMMUNOREGULATION IN PARTICLEINDUCED LUNG FIBROSIS