An αvβ3 integrin checkpoint is critical for efficient T(H)2 cytokine polarisation and potentiating antigen-specific immunity
Publication details: 2023-01.Subject(s): Genre/Form: Online resources: Summary: Naïve CD4(+) T lymphocytes initially undergo antigen-specific activation to promote a broad-spectrum response before adopting bespoke cytokine expression profiles shaped by intercellular microenvironmental cues, resulting in pathogen-focussed modular cytokine responses. Interleukin (IL)-4-induced Gata3 upregulation is important for the T helper 2 (T(H)2) cell polarisation associated with anti-helminth immunity and misdirected allergic inflammation. Whether additional microenvironmental factors participate is unclear. Using whole mouse-genome CRISPR-Cas9 screens we discovered a previously unappreciated role for αvβ3 integrin in T(H)2 cell differentiation. Low-level αvβ3 expression by naïve CD4(+) T cells contributed to pan-T cell activation by promoting T-T cell clustering and IL-2/CD25/STAT5-signalling. Subsequently, IL-4/Gata3-induced selective upregulation of αvβ3 licenced intercellular αvβ3-Thy1 interactions among T(H)2 cells, enhanced mTOR signalling, supported differentiation and promoted IL-5/IL-13 production. In mice, αvβ3 was required for efficient allergen-driven antigen-specific lung T(H)2 cell responses. Thus, αvβ3-expressing T(H)2 cells form multicellular factories to propagate and amplify T(H)2 responses./pmc/articles/PMC7614022/
/pubmed/36550322
Naïve CD4(+) T lymphocytes initially undergo antigen-specific activation to promote a broad-spectrum response before adopting bespoke cytokine expression profiles shaped by intercellular microenvironmental cues, resulting in pathogen-focussed modular cytokine responses. Interleukin (IL)-4-induced Gata3 upregulation is important for the T helper 2 (T(H)2) cell polarisation associated with anti-helminth immunity and misdirected allergic inflammation. Whether additional microenvironmental factors participate is unclear. Using whole mouse-genome CRISPR-Cas9 screens we discovered a previously unappreciated role for αvβ3 integrin in T(H)2 cell differentiation. Low-level αvβ3 expression by naïve CD4(+) T cells contributed to pan-T cell activation by promoting T-T cell clustering and IL-2/CD25/STAT5-signalling. Subsequently, IL-4/Gata3-induced selective upregulation of αvβ3 licenced intercellular αvβ3-Thy1 interactions among T(H)2 cells, enhanced mTOR signalling, supported differentiation and promoted IL-5/IL-13 production. In mice, αvβ3 was required for efficient allergen-driven antigen-specific lung T(H)2 cell responses. Thus, αvβ3-expressing T(H)2 cells form multicellular factories to propagate and amplify T(H)2 responses.
https://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
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