STAT3 signaling modulates the immune response induced after antigen targeting to conventional type 1 dendritic cells
Fernando Bandeira Sulczewski1, Larissa Alves Martino1, Davi Salles1
1Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil.
Insights
STAT3 signaling does not impact Tfh cell responses from cDC2. However, it is crucial for cDC1 to promote Th1 and Tfh cell responses, highlighting STAT3
Area of Science:
- Immunology
- Cell Biology
- Signaling Pathways
Background:
- Conventional dendritic cells (cDC) prime T cell responses.
- Splenic cDC are divided into cDC1 (prime Th1) and cDC2 (prime Tfh).
- Mechanisms controlling cDC1 and cDC2 functions, especially STAT3 signaling, are not fully understood.
Purpose of the Study:
- Investigate the role of STAT3 signaling in cDC1 and cDC2 function.
- Determine how STAT3 modulates CD4+ T cell priming by cDC1 and cDC2.
- Utilize targeted antigen delivery via DEC205 (cDC1) and DCIR2 (cDC2) receptors.
Main Methods:
- Antigen targeting to cDC1 via DEC205 and cDC2 via DCIR2.
- Comparison of CD4+ T cell responses in STAT3-deficient and wild-type mice.
- Analysis of Tfh and Th1 cell frequencies.
Main Results:
- STAT3 deficiency did not alter Tfh cell induction by cDC2 targeting.
- STAT3 deficiency significantly reduced Th1 and Tfh cell responses after cDC1 targeting.
- STAT3 signaling is dispensable for cDC2-mediated Tfh induction but modulates cDC1 function.
Conclusions:
- STAT3 signaling is not essential for cDC2 to promote Tfh responses via DCIR2.
- STAT3 signaling modulates cDC1 function in promoting Th1 and Tfh responses via DEC205.
- STAT3 plays a differential role in cDC1 and cDC2 mediated T cell priming.
Abstract:
Conventional dendritic cells (cDC) are a group of antigen-presenting cells specialized in priming T cell responses. In mice, splenic cDC are divided into conventional type 1 DC (cDC1) and conventional type 2 (cDC2). cDC1 are specialized to prime the Th1 CD4+ T cell response, while cDC2 are mainly associated with the induction of follicular helper T cell responses to support germinal center formation. However, the mechanisms that control the functions of cDC1 and cDC2 are not fully understood, especially the signaling pathways that can modulate their ability to promote different CD4+ T cell responses. Here, we targeted a model antigen for cDC1 and cDC2, through DEC205 and DCIR2 receptors, respectively, to study the role of the STAT3 signaling pathway in the ability of these cells to prime CD4+ T cells. Our results show that, in the absence of the STAT3 signaling pathway, antigen targeting to cDC2 induced similar frequencies of Tfh cells between STAT3-deficient mice compared to fully competent mice. On the other hand, Th1 and Th1-like Tfh cell responses were significantly reduced in STAT3-deficient mice after antigen targeting to cDC1 via the DEC205 receptor. In summary, our results indicate that STAT3 signaling does not control the ability of cDC2 to promote Tfh cell responses after antigen targeting via the DCIR2 receptor, but modulates the function of cDC1 to promote Th1 and Th1-like Tfh T cell responses after antigen targeting via the DEC205 receptor.
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