The role of the acquired immune response in systemic sclerosis

Abstract

Profound alterations characterize the adaptive immune response in systemic sclerosis, and several layers of evidence support a prominent role exerted by immune cellular effectors and humoral mediators in the pathogenesis of this disease. These include (i) the presence of oligoclonal T cells in tissues undergoing fibrosis consistent with (auto)antigen-specific recruitment, (ii) the preferential expansion of polarized CD4+ and CD8+ T cells producing pro-fibrotic cytokines such as IL-4 and IL-13, (iii) the presence of increased number of cells producing mediators belonging to the IL-17 family, including IL-22, which may drive and participate in inflammatory pathways involving epithelial cells as well as fibroblasts, (iv) the deficient or redirected function of T regulatory cells favoring fibrosis, and (v) the enhanced expression of CD19 and CD21 on naïve B cells, and the upregulation of co-stimulatory molecules in mature B cells, which together with the increased levels of B cell activating factor (BAFF) underlie the propensity to an exaggerated humoral response possibly favoring fibrogenesis. Despite all the progress made in understanding the features of the aberrant immune response in scleroderma, it remains unclear whether the activation of immune effector pathways ultimately drives the disease pathogenesis or rather represents a defective attempt to limit or even reverse excessive extracellular matrix deposition and progressive vasculopathy, the main hallmarks of this disease.

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

“…Numerous studies have demonstrated strong evidence for the role of cell‐mediated immunity (CMI) in SSc . Recent studies have shown that alterations in CMI are important participants in GIT involvement in SSc.…”

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

“…Patients with SSc also present an abnormal activation of T and B cells (62). T cells in skin lesions are predominantly CD4 + T cells.…”

Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration

“…Specific populations of lymphocytes, the effector cells of adaptive immunity activated by monocyte-derived antigen-presenting cells during inflammation, are also clearly involved in mammalian tissue fibrosis (scarring) and fibrotic disorders (Wynn, 2004). Many details of the mechanisms by which lymphocytes promote injury-related fibrosis are active areas of investigation and beyond the scope of this review, but both T H 2-type and T H 17-type immune responses are proinflammatory and profibrotic, and cytokines in the IL-17 family have emerged as important drivers of postinflammatory fibrosis in many organs (Chizzolini & Boin, 2015;Kirkham, Kavanaugh, & Reich, 2014;Wynn & Ramalingam, 2012) and during allograft rejection (Liu, Fan, & Jiang, 2013). Cytotoxic T cells and other effectors of adaptive immunity may also directly eliminate genetically reprogrammed cells that express "embryonic" or other neoantigens recognized as "non-self" and arise early in the transition from inflammation to regeneration (Quigley & Kristensen, 2015).…”