Innate and Adaptive Interleukin-17–producing Lymphocytes in Chronic Inflammatory Lung Disorders

Abstract

During T-cell receptor activation in a particular cytokine environment, naive CD4+ T cells may differentiate into lineages defined by their pattern of cytokine production and transcription factors: T helper type 1 (Th1), Th2, Th17, and Th22 cells; follicular helper T cells; and inducible regulatory T cells. Th17 cells have been recognized as a distinct lineage of Th cells, and associations between IL-17 and human disease have been known somewhat longer. It would be an oversimplification to restrict IL-17 to Th17 cells. Indeed, IL-17 is also expressed by other cells including IL-17-producing γδ T (γδ T-17) cells, natural killer T-17 cells, and IL-17-producing lymphoid tissue-induced cells. IL-17 was cloned in 1995 as a cytokine expressed by T cells, exerting inflammatory effects on epithelial, endothelial, and fibroblast cells. IL-17 is a solid link between innate and adaptive immunity and can exert both beneficial and deleterious effects. The discovery of IL-17 T cells has provided exciting new insights into host defense, immunoregulation, and autoimmunity. Unquestionably, data from mouse models have contributed enormously to our insight into immunological mechanisms. However, because of numerous differences between murine and human immunology, data obtained in mice are not simply interchangeable. We review IL-17 T cells exclusively in the human situation and more specifically their potential role in respiratory diseases. The advances in our understanding of IL-17 regulation offer opportunities to dissect the human IL-17 system and to reflect on the clinical presentation of lung diseases. More importantly, the IL-17 system allows us to speculate on new therapeutic opportunities. Some results have been previously reported in an abstract.

CD19+CD21low B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome

“…Severe neutrophilic inflammation was observed in the early phase of BOS, whereas prolonged immune activation is known to induce a fibrotic process resulting in airway obliteration. 45 During airway wall destruction, bronchus-associated lymphoid tissue is generated and B cells generate autoimmune antibodies as reported against collagen V. 46 Srinivasan et al 47 observed CD4 1 T-cell and donor-derived B220 1 B-cell infiltrations with alloantibody deposition in murine lungs with BO after HCT. In our BOS cohort, BAFF levels and the BAFF/B-cell ratio were significantly higher compared with patients without cGVHD.…”

T helper cell populations: As flexible as the skin?

“…In addition, IL-22 also signals in a similar manner as IL-10, since they both activate STAT3, but IL-22 may also activate other pathways such as MAP kinase, and thus induce additional inflammatory signals [32]. IL-22 is produced by different immune cells, including certain Th17 cells, gd T cells and innate lymphoid cells [33], which is similar to the cellular sources of IL-17 [34]. Like IL-17, IL-22 is mainly produced by the adaptive immune system but its receptor is mostly expressed by nonhematopoietic cells.…”

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

“…Advances in understanding the effects of allograft cellular senescence (accelerated ageing) on allograft function and BOS risk are needed, and a better understanding of the role of interleukin-17 [150][151][152][153][154][155][156], autoimmune pathways, regulatory lymphocyte populations [157][158][159][160][161][162][163] and neutrophil responses, as well as mechanisms by which the hypothetical phenomenon of epithelial-mesenchymal transition (which remains hypothetical and has not been well validated in humans) [164][165][166][167] leads to airway fibrosis, may lead to novel therapies to prevent and treat BOS. Improved animal models of OB are needed and are likely to be useful in improving our understanding of the role of these and other phenomena in the initiation, progression, prevention and treatment of OB following lung transplantation.…”