Eosinophils in Autoimmune Diseases

Abstract

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

Blood eosinophil levels and prognosis of hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease

“…About 37% of patients with COPD display a persistently elevated eosinophil count [14]. Despite the association of eosinophils with inflammatory and autoimmune diseases, the exact clinical implications of those elevated counts in COPD remain controversial [24,25]. On the one hand, the Copenhagen City Lung study showed that eosinophil count >340 cells/µL were associated with a higher risk of AECOPD, but that the threshold of 2% was not [17], as supported by Singh et al [14] and Zysman et al [18].…”

“…Eosinophils play important roles in inflammatory diseases, especially the initiation and modulation of inflammation [24]. Their role in diseases like asthma has been known for a long time, but they are now known to play roles in diseases like COPD, inflammatory bowel diseases, autoimmune myocarditis, and primary biliary cirrhosis, among others [10-13, 24, 25].…”

“…Their role in diseases like asthma has been known for a long time, but they are now known to play roles in diseases like COPD, inflammatory bowel diseases, autoimmune myocarditis, and primary biliary cirrhosis, among others [10-13, 24, 25]. The mechanisms for their association with autoimmune diseases include degranulation of their granule content, autoantibodydependent cell-mediated cytotoxicity, degradation of the extracellular matrix, cytokine secretion, antigen presentation, induction of fibrosis; and role in thrombosis [24,25]. Patients with underlying eosinophil-associated diseases might be at higher risk of autoimmune diseases [24][25][26][27].…”

Informed dimension reduction of clinically-related genome-wide association summary data characterises cross-trait axes of genetic risk

“…38 Our results suggest eosinophilic involvement in a wide variety of autoimmune diseases, in addition to inflammatory diseases, in agreement with other recent findings. 39 IP-10 and MIG are chemokines, secreted by epithelial and dendritic cells (amongst others), which act as chemoattractants for immune cells which express the receptor CXCR3, including Th1 cells. Both MIG and IP-10 expression at the site of autoimmune target have been implicated in the development of autoimmunity 40,41 and IP-10 has been observed to be upregulated in follicular cells of patients with myasthenia gravis.…”

Murine eosinophil development and allergic lung eosinophilia are largely dependent on the signaling adaptor GRB2

“…Eosinophil‐associated disorders range from allergic inflammation to autoimmunity and hypereosinophilic syndrome that may result in eosinophil‐mediated tissue damage including lung damage, ulcerative colitis, esophagitis, and myocarditis . A better understanding of eosinophil development, homeostasis and effector functions is critical to develop efficient therapeutic options that lower the number and activity of these cells in different pathologic conditions .…”