Basophils are granulocytes that exist at a relatively rare frequency in the blood but dysregulated function of these cells is a key feature of allergic and several inflammatory responses. An important question that is not yet addressed in-depth is the process and mechanisms that check the activation of basophils.
Our initial hypothesis was that CD4+CD25+FoxP3+ regulatory T cells (Tregs) that are key mediators of immune tolerance might keep basophil activation in check. There were indeed valid reasons behind this perception as Tregs are already well characterized for their inhibitory action on diverse immune cells of both innate and adaptive immune compartments like macrophages, dendritic cells, monocytes, natural killer cells, neutrophils, mast cells, T lymphocytes and B lymphocytes. Thus, a general belief in the immunology community is that no immune cell could escape suppression by Tregs.
Contrary to our initial hypothesis and belief, our team has found that human basophils are refractory to Treg-mediated suppression. Unexpectedly, we further noticed that Tregs were able to activate the basophils to induce the expression of various activation markers such as CD69, CD203c, and CD13 and the release of cytokines IL-13, IL-8, and IL-4. Although Tregs themselves did not induce degranulation and release of histamine by basophils, they sensitized the basophils to receive FcεRI-mediated degranulation signals.
We then aimed at exploring the mechanisms by which Tregs induce basophil activation. Our data revealed that Tregs induce basophil activation by a process that was not contact-dependent rather it was mediated by Treg-derived IL-3 that signals subsequent STAT5 activation in basophils. Inhibition of IL-3 signaling either by blockade of IL-3 receptor on basophils or by using inhibitors of STAT5 activation abrogated Treg-induced basophil activation.
To our knowledge, our results provide first ever evidence that Tregs are not always immunosuppressive. They can also have positive effects on the activation of a particular immune cell. Our report thus reveals a covert relationship of human basophils and Tregs.
Sharma M, Das M, Stephen-Victor E, Galeotti C, Karnam A, Maddur MS, Bruneval P, Kaveri SV, Bayry J. Regulatory T cells induce activation rather than suppression of human basophils. Sci Immunol. 2018 May 25;3(23). pii: eaan0829. doi: 10.1126/sciimmunol.aan0829.
Jagadeesh Bayry, DVM, PhD, HDR
Scientist CRCN/Associate Professor-INSERM
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1138
Centre de Recherche des Cordeliers
15, Rue de l’Ecole de Médecine