Abstract Background Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by segmental and transmural inflammation that can affect any part of the gastrointestinal tract. In pediatric CD, this discontinuous and variable involvement of gut regions suggests region-specific immune dysregulation. However, how local immune responses differ across intestinal sites, and how they integrate with systemic immunity to drive disease pathology, remains poorly understood. Understanding these spatial immune alterations is critical for elucidating CD pathogenesis and identifying regionally tailored therapeutic strategies. Methods We performed single-cell RNA sequencing of intestinal tissues and paired peripheral blood mononuclear cells from 11 treatment-naïve pediatric Crohn’s disease patients and 6 healthy controls. Tissue samples were collected from up to four gut regions—terminal ileum, ascending colon, descending colon, and rectum—including lesional and non-lesional sites, enabling integrated tissue–blood immune profiling. Results We observed an increased proportion and elevated activation of Th1 cells in the lesional tissues of CD patients compared to healthy controls. Within the Th1 compartment, regional analysis revealed that the rectal lesion exhibited the highest Th1 cell proportion and strongest expression of IFNG. A cytotoxic T helper cell signature, marked by elevated expression of IFNG, TBX21, PRF1, GZMB, SLAMF7, and HOPX, was also most prominently enriched in the rectal region, suggesting a region-specific enhancement of Th1 cytotoxicity in CD lesions. Conclusion Our findings highlight a regionally enriched Th1 cell response in the rectum of treatment-naïve pediatric Crohn’s disease, suggesting a potential cellular contributor to local inflammation and a candidate target for future therapeutic intervention. Our findings highlight a regionally enriched Th1 cell response in the rectum of treatment-naïve pediatric Crohn’s disease, suggesting a potential cellular contributor to local inflammation and a candidate target for future therapeutic intervention. Conflict of interest: Mr. Lim, Jin Gyu: No conflict of interest Cha, Seung Min: No conflict of interest Kim, Hyun Je: No conflict of interest Shim, Jung Ok: No conflict of interest Moon, Jin Soo: No conflict of interest
Lim et al. (Thu,) studied this question.