Che You, Han Jungmin, Harkins Catriona P, Hou Peng, Conlan Sean, Deming Clay, Amirkhani Adel, Bingham Molly A, Holmes Cassandra J, Englander Hanna, Shen Zeyang, Castelo-Soccio Leslie, Dimitrova Dimana, Kanakry Jennifer A, Bergerson Jenna R E, Notarangelo Luigi D, Pittaluga Stefania, Zhao Chen, Dell'Orso Stefania, Pai Sung-Yun, Hickstein Dennis D, Holland Steven M, Brownell Isaac, Nagao Keisuke, Gonzalez Corina E, Shah Nirali N, Freeman Alexandra F, Su Helen C, Segre Julia A, Kong Heidi H
Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Cell Host Microbe. 2025 Jul 24. doi: 10.1016/j.chom.2025.07.002.
The human skin microbiome is intricately intertwined with host immunity. While studies have elucidated microbial influences on immunity, understanding how immune alterations modulate this equilibrium remains limited. We investigated the dual impact of immune deficiency and hematopoietic stem cell transplantation (HSCT) on the skin microbiome in 24 patients with dedicator of cytokinesis 8 (DOCK8) deficiency, a rare inborn error of immunity. Analyzing 590 metagenomic and 534 16S rDNA sequencing samples across eight skin sites, we observed disrupted microbiota pre-HSCT (median eukaryotic viruses 67.6% vs. 0.04% in controls), with extremely diverse human papillomaviruses (HPVs) and polyomaviruses-including oncogenic viruses. Specific bacterial species markedly changed, including decreased Staphylococcus aureus post-HSCT. DNA eukaryotic viruses dramatically decreased (79.7% ± 28.3% to 4.9% ± 8.6%; p < 0.01) 12 months post-HSCT. Recovered microbial communities remained relatively stable through 1-year follow-up with clearance of oncogenic HPV and no convergence with transplant donors. These results highlight the immune system's critical role in restoring microbial balance and skin health.
人类皮肤微生物群与宿主免疫密切相关。虽然已有研究阐明了微生物对免疫的影响，但对于免疫改变如何调节这种平衡的了解仍然有限。我们调查了免疫缺陷和造血干细胞移植（HSCT）对24例细胞分裂素8（DOCK8）缺陷患者皮肤微生物群的双重影响，DOCK8缺陷是一种罕见的先天性免疫缺陷病。通过分析八个皮肤部位的590个宏基因组和534个16S rDNA测序样本，我们观察到HSCT前微生物群紊乱（真核病毒中位数为67.6%，而对照组为0.04%），其中人类乳头瘤病毒（HPV）和多瘤病毒种类极为多样，包括致癌病毒。特定细菌种类发生显著变化，包括HSCT后金黄色葡萄球菌减少。HSCT后12个月，DNA真核病毒显著减少（从79.7%±28.3%降至4.9%±8.6%；p<0.01）。在为期1年的随访中，恢复的微生物群落保持相对稳定，致癌HPV清除，且未与移植供体趋同。这些结果突出了免疫系统在恢复微生物平衡和皮肤健康方面的关键作用。
