Razvozlavanje vloge izločanja IL4i1 iz dendritičnih celic z visoko ekspresijo receptorja CD5

Dendritic cells (DCs) are essential professional antigen-presenting cells that play a critical role in connecting the innate and adaptive immune systems by influencing T cell activation and differentiation. This thesis investigated the interplay between IL4i1, a potential immunomodulatory enzyme associated with tumor progression, and CD5$^{high}$ expressing dendritic cells, which have been linked to enhanced T cell priming and improved survival outcomes in cancer patients. Given the opposing roles of IL4i1 and CD5$^{high}$ expressing DCs, the primary hypothesis was that CD5$^{high}$ expressing DCs do not express IL4i1 or that the expression levels are lower than in normal DCs. To test this hypothesis, CD5$^{high}$ expressing DCs were generated in vitro from mouse bone marrow using a low concentration of the cytokine IL-6 (5 ng/ mL) during the DC differentiation process. The results demonstrated that CD5$^{high}$ expressing DCs indeed displayed reduced IL4i1 expression at both the protein and mRNA levels. This downregulation may be linked to signaling pathways activated by IL-6, which could inhibit IL4i1 production while promoting the differentiation of CD5$^{high}$ expressing DCs. Further experiments revealed that the timing of IL-6 addition during the differentiation process influenced IL4i1 expression, with earlier administration leading to greater downregulation. Additionally, the effects of IL-6 on the differentiation of conventional DC subsets, particularly cDC1s and cDC2s, as well as the expression of CD5, were explored. The findings indicated that IL-6 inhibits cDC1 differentiation while also upregulating CD5 expression. Specifically, the earlier addition of IL-6 during DC differentiation resulted in greater inhibition of cDC1 differentiation and increased CD5 expression. Notably, while IL-10 also activated the JAK/STAT3 pathway, it did not replicate the downregulation of IL4i1 observed with IL-6, suggesting the involvement of alternative regulatory mechanisms specifically activated by IL-6. Moreover, inhibiting the JAK/STAT3 signaling pathway using Ruxolitinib did not reverse the IL-6 downregulation effect on IL4i1 expression, indicating other mechanisms' potential involvement. These insights into the relationship between IL4i1 and CD5$^{high}$ expressing DCs provide a foundational understanding of the biological mechanisms involved. However, further experimentation is needed to elucidate this field more comprehensively and explore the potential medical implications.