Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
PLoS One. 2011;6(8):e22848. doi: 10.1371/journal.pone.0022848. Epub 2011 Aug 3.
IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21(low)CD38(low)). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies.
IL-17 是一种促炎细胞因子，与自身免疫和炎症状态有关。IL-17 产生的 CD4 T 细胞（Th17）的发育/存活与 B 细胞分化共享关键线索，最近表明循环滤泡辅助 T 细胞亚群富含能够帮助 B 细胞分化的 Th17 细胞。我们通过研究原发性 B 细胞免疫缺陷中的 Th17 细胞区室来研究 Th17 细胞稳态与 B 细胞之间的潜在联系。常见可变免疫缺陷症（CVID）是由 B 细胞分化为浆细胞和记忆 B 细胞的缺陷定义的，常与自身免疫和炎症表现相关，但我们没有发现这些与 Th17 细胞频率之间存在关系。事实上，CVID 患者的 Th17 细胞频率与激活的未分化 B 细胞（CD21(low)CD38(low)）的扩张平行下降。此外，由于早期 B 细胞发育受损而缺乏 B 细胞的先天性无丙种球蛋白血症患者，循环 Th17 细胞严重减少。最后，我们在健康个体中发现，循环 Th17 细胞频率与转换型记忆 B 细胞和血清 BAFF 水平之间存在直接相关性，BAFF 是 B 细胞存活的关键细胞因子。总的来说，我们的数据支持 Th17 细胞稳态与 B 细胞成熟之间的关系，这对理解炎症/自身免疫性疾病的发病机制和 B 细胞耗竭疗法的生理学具有重要意义。
