Regulatory T cells induce activation rather than suppression of human basophils

Meenu Sharma (1) , Mrinmoy Das (2) , Emmanuel Stephen-Victor (2) , Caroline Galeotti (2) , Anupama Karnam (2) , Mohan S Maddur (2) , Patrick Bruneval (3) , Srini Kaveri (2) , Jagadeesh Bayry (4)

1 GEC - Génie Enzymatique et Cellulaire
2 CRC - Centre de Recherche des Cordeliers
3 Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou]
4 USPC - Université Sorbonne Paris Cité

Basophils are a rare granulocyte population that have been associated with allergic and inflammatory responses. It is essential to understand the regulatory mechanisms by which basophils are kept in check, considering the impact of dysregulated basophil function on immune responses under different pathological conditions. Among immunoregulatory cells, CD4+CD25+FoxP3+ regulatory T cells (Tregs) are the key players that maintain immune tolerance. The mechanisms by which Tregs regulate and suppress diverse immune cell subsets have been studied extensively, but the impact of Tregs on basophil functions is not well understood. We report that human basophils are refractory to Treg-mediated suppression and found that Tregs stimulate resting basophils to induce the expression of activation markers including CD69, CD203c and CD13, and the release of basophil cytokines including IL-13, IL-8 and IL-4. Mechanistically, Tregs could induce human basophil activation via IL-3 and STAT5 activation, whereas cellular contact was dispensable. Inhibition of either IL-3-IL-3 receptor interactions or STAT5 phosphorylation abrogated Treg-mediated activation of basophils. These results provide evidence of direct positive effects that human Tregs have on basophil activation and reveal a previously unrecognized feature of this cell subset well known for immunosuppressive functions.

Domaines: Immunité innée; Allergologie

Meenu Sharma, Mrinmoy Das, Emmanuel Stephen-Victor, Caroline Galeotti, Anupama Karnam, et al.. Regulatory T cells induce activation rather than suppression of human basophils. Science Immunology, 2018, 3 (23), pp.eaan0829. ⟨10.1126/sciimmunol.aan0829⟩. ⟨hal-01818723⟩