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. Author manuscript; available in PMC: 2020 Jan 1.
Published in final edited form as: Curr Rheumatol Rev. 2019;15(4):277–289. doi: 10.2174/1573397115666190116102451

Figure 2: Theory of progressive ILD development.

Figure 2:

Systemic inflammation leads to the production of inflammatory cytokines, such as TNF-α and INF-γ. These factors circulate and act on the lung, where they induce the upregulation of several adhesion factors, such as P and E selectin, and ICAM-1. These ultimately lead to the recruitment and extravasation of circulating monocytes/macrophages, while the cytokines continue to activate tissue-resident inflammatory cells such as alveolar macrophages. With the activation of the local environment, the tissue is primed for exacerbation by an external antigen, such as cigarette smoke. Once there is antigen presentation, a secondary immune response is activated, leading to the recruitment and activation of T and B cells, thereby resulting in ACPA production. Antigen-presentation and activation of the macrophage and DC populations can also induce the expression of TGF-β, which activates local fibroblasts and leads to collagen deposition, resulting in fibrosis.