Datasets	Category	Treg source	Type	TotalDEG	Exo up	/DEG%	Exo down	/DEG%
GSE119169	Lymphoid	Spleen	Array	44	9	20.45	5	11.36
GSE37532	Lymphoid	Lymph node	Array	397	116	29.22	24	6.05
E-MTAB-7961	Lymphoid	Spleen	RNA-seq	1802	301	16.70	107	5.94
GSE20366	Non-lymphoid	Small intestinal lamina propria	Array	756	189	25.00	165	21.83
GSE64909	Non-lymphoid	Brown adipose tissue	Array	113	55	48.67	5	4.42
GSE37532	Non-lymphoid	Visceral adipose tissue(VAT)	Array	924	254	27.49	85	9.20
E-MTAB-7961	Non-lymphoid	Kidney	RNA-seq	1584	356	22.47	174	10.98

The DEGs belong to the exosome genes in each Treg datasets were analyzed by IPA. Upregulated commonly shared exosome pathways in normal tissues were shown below. A total of 56 exosome pathways were enriched in normal Treg groups, including 22 commonly shared and 34 specific pathways. Synaptic Long Term Depression and Role of NFAT in Regulation of the Immune Response were common in lymphoid tissue Treg. Cardiac Hypertrophy Signaling, Sphingosine-1-phosphate Signaling and Wnt/Ca+ pathway were common in non-lymphoid tissue Treg. Production of Nitric Oxide and Reactive Oxygen Species in Macrophages was enriched in GSE37532 lymph node Treg. Neuroinflammation Signaling Pathway, Type I Diabetes Mellitus Signaling, ERK5 Signaling, NF-κB Signaling Synaptic Long Term Potentiation, and Endothelin-1 Signaling were enriched in E-MTAB-7961 spleen Treg. Vitamin-C Transport, FGF Signaling,and Senescence Pathway were enriched in GSE37532 VAT Treg. 24 pathways enriched in E-MTAB-7961 kidney were shown in Supplementary Table 6A (cut off: p < 0.05 and |Z-score| >= 2).