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Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice

Heleen Vroman, Denise van Uden, Ingrid M. Bergen, Jennifer A.C. van Hulst, Melanie Lukkes, Geert van Loo (UGent) , Björn E. Clausen, Louis Boon, Bart Lambrecht (UGent) , Hamida Hammad (UGent) , et al.
(2020) ALLERGY. 75(10). p.2587-2598
Author
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Abstract
BACKGROUND: Conventional type 1 dendritic cells (cDC1s) control antiviral and antitumor immunity by inducing antigen-specific cytotoxic CD8+ T-cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF-κB, might determine the precise outcome of Th-cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2-driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF-κB signaling METHODS: To target pulmonary cDC1s, Cd207 (Langerin)-mediated excision of A20/Tnfaip3 was used, generating Tnfaip3fl/fl xCd207+/cre (Tnfaip3Lg-KO ) mice. Mice were exposed to house dust mite (HDM) to provoke Th2-mediated immune responses. RESULTS: Mice harboring Tnfaip3-deficient cDC1s did not develop Th2-driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ-expressing CD8+ T-cells. In addition, Tnfaip3Lg-KO mice harbored increased numbers of IL-12-expressing cDC1s and elevated PD-L1 expression in all pulmonary DC subsets. Blocking either IL-12 or IFNγ in Tnfaip3Lg-KO mice restored Th2-responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2-development. CONCLUSIONS: These findings indicate that the activation status of cDC1s, shown by their specific expression of co-inhibitory molecules and cytokines, critically contributes to the development of Th2-cell-mediated disorders, most likely by influencing IFNγ production in CD8+ T-cells.
Keywords
Immunology, Immunology and Allergy, A20, Tnfaip3, CD8(+) T cells, interferon gamma, Th2&#8208, driven airway inflammation, Type 1 conventional dendritic cells, IFN-GAMMA, CONSTITUTIVE EXPRESSION, IMMUNE-RESPONSES, INHALED ANTIGEN, TH2 RESPONSES, CD103(+), LUNG, ASTHMA, DUST, A20

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MLA
Vroman, Heleen, et al. “Tnfaip3 Expression in Pulmonary Conventional Type 1 Langerin‐expressing Dendritic Cells Regulates T Helper 2‐mediated Airway Inflammation in Mice.” ALLERGY, vol. 75, no. 10, 2020, pp. 2587–98, doi:10.1111/all.14334.
APA
Vroman, H., van Uden, D., Bergen, I. M., van Hulst, J. A. C., Lukkes, M., van Loo, G., … Kool, M. (2020). Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice. ALLERGY, 75(10), 2587–2598. https://doi.org/10.1111/all.14334
Chicago author-date
Vroman, Heleen, Denise van Uden, Ingrid M. Bergen, Jennifer A.C. van Hulst, Melanie Lukkes, Geert van Loo, Björn E. Clausen, et al. 2020. “Tnfaip3 Expression in Pulmonary Conventional Type 1 Langerin‐expressing Dendritic Cells Regulates T Helper 2‐mediated Airway Inflammation in Mice.” ALLERGY 75 (10): 2587–98. https://doi.org/10.1111/all.14334.
Chicago author-date (all authors)
Vroman, Heleen, Denise van Uden, Ingrid M. Bergen, Jennifer A.C. van Hulst, Melanie Lukkes, Geert van Loo, Björn E. Clausen, Louis Boon, Bart Lambrecht, Hamida Hammad, Rudi W. Hendriks, and Mirjam Kool. 2020. “Tnfaip3 Expression in Pulmonary Conventional Type 1 Langerin‐expressing Dendritic Cells Regulates T Helper 2‐mediated Airway Inflammation in Mice.” ALLERGY 75 (10): 2587–2598. doi:10.1111/all.14334.
Vancouver
1.
Vroman H, van Uden D, Bergen IM, van Hulst JAC, Lukkes M, van Loo G, et al. Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice. ALLERGY. 2020;75(10):2587–98.
IEEE
[1]
H. Vroman et al., “Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice,” ALLERGY, vol. 75, no. 10, pp. 2587–2598, 2020.
@article{8660977,
  abstract     = {{BACKGROUND:
Conventional type 1 dendritic cells (cDC1s) control antiviral and antitumor immunity by inducing antigen-specific cytotoxic CD8+ T-cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF-κB, might determine the precise outcome of Th-cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2-driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF-κB signaling 

METHODS: 
To target pulmonary cDC1s, Cd207 (Langerin)-mediated excision of A20/Tnfaip3 was used, generating Tnfaip3fl/fl xCd207+/cre (Tnfaip3Lg-KO ) mice. Mice were exposed to house dust mite (HDM) to provoke Th2-mediated immune responses.

RESULTS:
Mice harboring Tnfaip3-deficient cDC1s did not develop Th2-driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ-expressing CD8+ T-cells. In addition, Tnfaip3Lg-KO mice harbored increased numbers of IL-12-expressing cDC1s and elevated PD-L1 expression in all pulmonary DC subsets. Blocking either IL-12 or IFNγ in Tnfaip3Lg-KO mice restored Th2-responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2-development.

CONCLUSIONS:
These findings indicate that the activation status of cDC1s, shown by their specific expression of co-inhibitory molecules and cytokines, critically contributes to the development of Th2-cell-mediated disorders, most likely by influencing IFNγ production in CD8+ T-cells.}},
  author       = {{Vroman, Heleen and van Uden, Denise and Bergen, Ingrid M. and van Hulst, Jennifer A.C. and Lukkes, Melanie and van Loo, Geert and Clausen, Björn E. and Boon, Louis and Lambrecht, Bart and Hammad, Hamida and Hendriks, Rudi W. and Kool, Mirjam}},
  issn         = {{0105-4538}},
  journal      = {{ALLERGY}},
  keywords     = {{Immunology,Immunology and Allergy,A20,Tnfaip3,CD8(+) T cells,interferon gamma,Th2&#8208,driven airway inflammation,Type 1 conventional dendritic cells,IFN-GAMMA,CONSTITUTIVE EXPRESSION,IMMUNE-RESPONSES,INHALED ANTIGEN,TH2 RESPONSES,CD103(+),LUNG,ASTHMA,DUST,A20}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2587--2598}},
  title        = {{Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice}},
  url          = {{http://doi.org/10.1111/all.14334}},
  volume       = {{75}},
  year         = {{2020}},
}
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