In my previous post I reviewed the role of microbiota and MyD88/TRIF pathway in CD103+ DC-derived TGF-β dependent IgA production. In the following review I will continue analyzing immunobiology of CD103+ DCs. Surprisingly, new paper published in JEM claims that CD103+ DCs naturally producing biologically active IL-12p70 restrain type II immunity during worm infection.
I have done some work on IL-12, so I was curious to review this paper. So lets begin. I will only show the data that I believe are relevant for the story. In first set of experiments, the authors showed that Batf3 -/- mice that lack CD103+ DCs have exaggerated type II response to S. mansoni eggs and worm infection itself (a typical Th2 trigger).
Similar exaggerated Th2 response were observed in Batf3 -/- mice infected with another Th2 trigger H. polygyrus.
More importantly, Batf3 -/- mice showed increased resistance to H. polygyrus infection.
To understand how Batf3-dependent CD103+ DCs influenced Th2 response, the authors analysed expression of IL-12, a cytokine known for its role in inhibiting Th2 response. Indeed, Batf3-dependent CD103+ DCs were main producers of steady-state IL-12 as measured by YFP expression under p40 promoter (p40 is a β chain of heterodimeric IL-12p70).
Finally, using bone marrow chimera, the authors showed that lack of biologically active IL-12 (IL-12p70) derived from Batf3-dependent CD103+ DCs was indeed responsible for exaggerated [and protective] Th2 response of Batf3-/- mice to H. polygyrus.
Of note, in separate set of experiments with germ-free and MyD88/TRIF DKO mice, the authors claim that Batf3-dependent CD103+ DCs were producing biologically active IL-12p70 independently of microbiota or TLR signaling. However, in contrast to YFP expression, flow staining pattern with antibody against p40 revealed little staining of IL-12p40 in CD103+ DCs from any of the mice analyzed. So, if not the data with IL-12p35-/-/Batf3-/- BM chimera, I would have dismissed this whole study as an artifact (to be convincing the authors need to show these results with p40-YFP mice on GF and MyD88/TRIF background).
In summary, this study suggests that Batf3-dependent CD103+ DC-derived IL-12p70 influences magnitude of type II immunity.
David Usharauli
More importantly, Batf3 -/- mice showed increased resistance to H. polygyrus infection.
To understand how Batf3-dependent CD103+ DCs influenced Th2 response, the authors analysed expression of IL-12, a cytokine known for its role in inhibiting Th2 response. Indeed, Batf3-dependent CD103+ DCs were main producers of steady-state IL-12 as measured by YFP expression under p40 promoter (p40 is a β chain of heterodimeric IL-12p70).
Finally, using bone marrow chimera, the authors showed that lack of biologically active IL-12 (IL-12p70) derived from Batf3-dependent CD103+ DCs was indeed responsible for exaggerated [and protective] Th2 response of Batf3-/- mice to H. polygyrus.
Of note, in separate set of experiments with germ-free and MyD88/TRIF DKO mice, the authors claim that Batf3-dependent CD103+ DCs were producing biologically active IL-12p70 independently of microbiota or TLR signaling. However, in contrast to YFP expression, flow staining pattern with antibody against p40 revealed little staining of IL-12p40 in CD103+ DCs from any of the mice analyzed. So, if not the data with IL-12p35-/-/Batf3-/- BM chimera, I would have dismissed this whole study as an artifact (to be convincing the authors need to show these results with p40-YFP mice on GF and MyD88/TRIF background).
In summary, this study suggests that Batf3-dependent CD103+ DC-derived IL-12p70 influences magnitude of type II immunity.
David Usharauli
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