TY - JOUR
T1 - Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
AU - Said, Elias A.
AU - Al-Dughaishi, Sumaya
AU - Al-Hatmi, Wadha
AU - Al-Reesi, Iman
AU - Al-Balushi, Mohammed S.
AU - Al-Bimani, Atika
AU - Al-Busaidi, Juma Z.
AU - Al-Riyami, Marwa
AU - Al-Khabori, Murtadha
AU - Al-Kindi, Salam
AU - Procopio, Francesco A.
AU - Al-Sinawi, Shadia
AU - Al-Ansari, Aliyaa
AU - Koh, Crystal Y.
AU - Al-Naamani, Khalid
AU - Al-Jabri, Ali A.
N1 - Publisher Copyright:
© 2023 Elias A. Said et al.
PY - 2023/10/9
Y1 - 2023/10/9
N2 - Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.
AB - Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.
KW - Humans
KW - Cytokines
KW - Dendritic Cells
KW - Midkine
KW - Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85174748449&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85174748449&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/9cb5edb8-9520-3b58-91b2-7d3faadd8fba/
U2 - 10.1155/2023/7944102
DO - 10.1155/2023/7944102
M3 - Article
C2 - 37850119
AN - SCOPUS:85174748449
SN - 2314-8861
VL - 2023
JO - Journal of Immunology Research
JF - Journal of Immunology Research
M1 - 7944102
ER -