TY  - BOOK
AU  - Szeto,Aydan C.H.
AU  - Ferreira,Ana C.F.
AU  - Mannion,Jonathan
AU  - Clark,Paula A.
AU  - Sivasubramaniam,Meera
AU  - Heycock,Morgan W.D.
AU  - Crisp,Alastair
AU  - Jolin,Helen E.
AU  - Kozik,Patrycja
AU  - Knolle,Martin D.
AU  - McKenzie,Andrew N.J.
TI  - An αvβ3 integrin checkpoint is critical for efficient T(H)2 cytokine polarisation and potentiating antigen-specific immunity
PY  - 2023///-01
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7614022; /pubmed/36550322
N2  - 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
UR  - http://dx.doi.org/10.1038/s41590-022-01378-w
ER  -