Cellular Complexity and Systemic Immune Profiles across Ancestral Diversity in Thailand and Mainland Southeast Asia
Sriwilai, B.; Nguantad, S.; Jevapatarakul, D.; Thungsatianpun, N.; Chantaraamporn, J.; Chaiwijit, P.; Asian Immune Diversity Atlas Network, ; Chatterjee, A.; Majumder, P. P.; Shin, J. W.; Ando, Y.; Park, J.-E.; Park, W.-Y.; Kock, K. H.; Tan, L. M.; Prabhakar, S.; Pithukpakorn, M.; Suktitipat, B.; Matangkasombut, P.; Charoensawan, V.
Show abstract
Mainland Southeast Asia (MSEA) remains under-represented in global immunogenomic references despite its extensive genetic heterogeneity. We present the first single-cell immune atlas of an MSEA population, utilizing Thai individuals from the Asian Immune Diversity Atlas (AIDA) as a representative cohort. We demonstrate that the Thai population is highly genetically diverse, reflecting its history as a geographic nexus for Asian admixture. By integrating single-cell transcriptomics with high-resolution genotyping, we show that genetic ancestry significantly shapes innate immune profiles, specifically CD14+ monocytes, highlighting potential evolutionary adaptations to regional pathogens. We identify specific sex-by-ancestry interactions that may drive the baseline activation of pro-inflammatory pathways in females, providing a long-sought cellular rationale for the high prevalence of autoimmune disorders observed in Southeast Asian populations. Ultimately, our study reveals that population-specific genetic architecture dictates immune heterogeneity often missed by self-reported ethnicity or country of origin, providing a critical immunogenomic reference for precision medicine in MSEA regions.
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