Alveolar macrophage–T cell interactions during Th1‐type sarcoid inflammation

Abstract

Sarcoidosis is an immunomediated, multisystem disorder of unknown cause(s) characterized by a heightened Th1 immune response that leads to an uncontrolled granuloma formation at sites of disease activity. The past few years have seen outstanding advances in the understanding of immunological and molecular events involved in the pathogenesis of this disease. The idea is that several cytokines and chemokines, which are secreted at sites of disease activity, participate in granuloma formation. This paper describes recent data that have clarified some of the events that govern the development of the hypersensitivity reaction during sarcoidosis. In particular, we will review recent evidence indicating that a complex relationship exists between the macrophage/lymphocyte cellular axis and the tissue networks of cytokines.

Alveolar macrophages are the main source for tumour necrosis factor‐α in patients with sarcoidosis

“…Notably, in the present study, Alveolar macrophages of patients with sarcoidosis exhibit multiple secretory cell functions in that they release other cytokines such as IL-15, growth factors, and chemokines such as monocyte chemotactic protein-1, RANTES (regulated, on activation, T-cell expressed and secreted) and macrophage inflammatory proteins-1a and -1b [2,26,27]. Thus, alveolar macrophages may strongly affect T-cell recruitment and T-cell response [28]. In turn, T-cells are also known to spontaneously release increased levels of some cytokines and chemokines, e.g.…”

CXCR3 ligands are augmented during the pathogenesis of pulmonary sarcoidosis

“…This is supported by studies finding CXCR3 expression on BAL lymphocytes from sarcoid patients [13]. Importantly, IL-2 has been found to be one of the most potent inducers of CXCR3 on lymphocytes [29], and multiple studies have suggested that IL-2 is pivotal in activating peripheral blood and BAL lymphocytes during pulmonary sarcoidosis [30][31][32][33][34].…”

“…This study was designed to determine whether there are augmented levels of IFN-inducible ELR -CXC chemokines in bronchoalveolar lavage fluid (BALF) from patients with the clinical/pathological diagnosis of pulmonary sarcoidosis, and resolve the current discrepancies within the literature [9][10][11][12][13]. Moreover, this study aimed to elucidate the cellular sources of specific IFN-inducible ELR -CXC chemokines and determine which cells express CXCR3 during the pathogenesis of pulmonary sarcoidosis.…”

“…Although an area of active investigation, the type 1 cytokine-chemokine network involved in the recruitment of mononuclear cells to the lungs of sarcoid patients has not been fully elucidated. We and other investigators have hypothesised that the CXCR3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung granulomas; however, significant discrepancies in the current literature remain [9][10][11][12][13]. In an effort to clarify previous conflicting findings, we performed the largest observational study to date of IFN-inducible ELR -CXC chemokines in sarcoid BALF.…”

Characterization of Human T Cells That Regulate Neutrophilic Skin Inflammation

“…In contrast, Th2 responses use the cytokines IL-5, IL-4, and IL-13, which enhance eosinophil and mast cell mobilization and cause certain allergic diseases such as asthma. In addition, Th1 responses may be counteracted by Th2 responses (1)(2)(3)(4)(5).…”