Serpinb1a Is Dispensable for the Development and Cytokine Response of Invariant Natural Killer T Cell Subsets

Leborgne, Nathan G. F.; Taddeo, Adriano; Freigang, Stefan; Benarafa, Charaf (2020). Serpinb1a Is Dispensable for the Development and Cytokine Response of Invariant Natural Killer T Cell Subsets. Frontiers in immunology, 11, p. 562587. Frontiers Research Foundation 10.3389/fimmu.2020.562587

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Invariant natural killer T (iNKT) cells are innate-like T lymphocytes. They quickly respond to antigenic stimulation by producing copious amounts of cytokines and chemokines. iNKT precursors differentiate into three subsets iNKT1, iNKT2, and iNKT17 with specific cytokine production signatures. While key transcription factors drive subset differentiation, factors that regulate iNKT subset homeostasis remain incompletely defined. Transcriptomic analyses of thymic iNKT subsets indicate that Serpinb1a is one of the most specific transcripts for iNKT17 cells suggesting that iNKT cell maintenance and function may be regulated by Serpinb1a. Serpinb1a is a major survival factor in neutrophils and prevents cell death in a cell-autonomous manner. It also controls inflammation in models of bacterial and viral infection as well as in LPS-driven inflammation. Here, we examined the iNKT subsets in neutropenic Serpinb1a -/- mice as well as in Serpinb1a -/- mice with normal neutrophil counts due to transgenic re-expression of SERPINB1 in neutrophils. In steady state, we found no significant effect of Serpinb1a-deficiency on the proliferation and numbers of iNKT subsets in thymus, lymph nodes, lung, liver and spleen. Following systemic activation with α-galactosylceramide, the prototypic glycolipid agonist of iNKT cells, we observed similar serum levels of IFN-γ and IL-4 between genotypes. Moreover, splenic dendritic cells showed normal upregulation of maturation markers following iNKT cell activation with α-galactosylceramide. Finally, lung instillation of α-galactosylceramide induced a similar recruitment of neutrophils and production of iNKT-derived cytokines IL-17, IFN-γ, and IL-4 in wild-type and Serpinb1a -/- mice. Taken together, our results indicate that Serpinb1a, while dominantly expressed in iNKT17 cells, is not essential for iNKT cell homeostasis, subset differentiation and cytokine release.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Leborgne, Nathan Georges François; Taddeo, Adriano; Freigang, Stefan Bernd and Benarafa, Charaf

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Stefan Bernd Freigang

Date Deposited:

11 Jan 2021 10:25

Last Modified:

17 Jan 2021 02:55

Publisher DOI:

10.3389/fimmu.2020.562587

PubMed ID:

33262755

Uncontrolled Keywords:

cytokine response; innate immunity; invariant NKT; serpin; α-galactosylceramide

BORIS DOI:

10.48350/151053

URI:

https://boris.unibe.ch/id/eprint/151053

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