Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ 07101, USA.
Institute for Immunology, Tsinghua University, Beijing 100084, China.
Cell Rep. 2018 Dec 4;25(10):2775-2783.e3. doi: 10.1016/j.celrep.2018.11.038.
Emphysema results in destruction of alveolar walls and enlargement of lung airspaces and has been shown to develop during helminth infections through IL-4R-independent mechanisms. We examined whether interleukin 17A (IL-17A) may instead modulate development of emphysematous pathology in mice infected with the helminth parasite Nippostrongylus brasiliensis. We found that transient elevations in IL-17A shortly after helminth infection triggered subsequent emphysema that destroyed alveolar structures. Furthermore, lung B cells, activated through IL-4R signaling, inhibited early onset of emphysematous pathology. IL-10 and other regulatory cytokines typically associated with B regulatory cell function did not play a major role in this response. Instead, at early stages of the response, B cells produced high levels of the tissue-protective protein, Resistin-like molecule α (RELMα), which then downregulated IL-17A expression. These studies show that transient elevations in IL-17A trigger emphysema and reveal a helminth-induced immune regulatory mechanism that controls IL-17A and the severity of emphysema.
肺气肿导致肺泡壁破坏和肺空气腔扩大，并已证明在寄生虫感染期间通过 IL-4R 独立机制发展。我们研究了白细胞介素 17A (IL-17A) 是否可以替代调节感染寄生虫 Nippostrongylus brasiliensis 的小鼠的肺气肿病理。我们发现，寄生虫感染后短暂的 IL-17A 升高会引发随后破坏肺泡结构的肺气肿。此外，通过 IL-4R 信号激活的肺 B 细胞抑制了肺气肿病理的早期发生。IL-10 和其他通常与 B 调节细胞功能相关的调节细胞因子在这种反应中没有发挥主要作用。相反，在反应的早期阶段，B 细胞产生高水平的组织保护蛋白 Resistin-like molecule α (RELMα)，然后下调 IL-17A 的表达。这些研究表明，IL-17A 的短暂升高会引发肺气肿，并揭示了一种寄生虫诱导的免疫调节机制，该机制控制 IL-17A 和肺气肿的严重程度。
