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Mucosal Immunol . Inflammatory chemokine receptors CCR1, CCR2, CCR3 and CCR5 are essential for an optimal T cell response to influenza

tetano

Editor, Senior Moderator
Mucosal Immunol


. 2025 May 23:S1933-0219(25)00052-2.
doi: 10.1016/j.mucimm.2025.05.005. Online ahead of print. Inflammatory chemokine receptors CCR1, CCR2, CCR3 and CCR5 are essential for an optimal T cell response to influenza

Marieke Pingen[SUP] 1 [/SUP], Catherine E Hughes[SUP] 2 [/SUP], Laura Medina-Ruiz[SUP] 2 [/SUP], Heather Mathie[SUP] 2 [/SUP], Jennifer A Barrie[SUP] 2 [/SUP], Chris Ah Hansell[SUP] 2 [/SUP], Robin Bartolini[SUP] 2 [/SUP], Megan Kl MacLeod[SUP] 2 [/SUP], Gerard J Graham[SUP] 3 [/SUP]



Affiliations
Free article Abstract

Inflammatory chemokine receptors CCR1/2/3/5 (iCCRs) play an important role in the recruitment of immune cells involved in innate immune functions and orchestrating the adaptive immune response. Here we utilise an influenza A virus (IAV) challenge to investigate the combinatorial roles of the iCCRs in the anti-IAV immune response. We did not observe any gross differences in infection-driven pathology in the absence of iCCRs. iCCR deletion resulted in decreased numbers of some antigen-presenting cell types in the lung (B cells, DC1s, monocytes and inflammatory macrophages), though cell numbers in the draining lymph node were not affected. Whilst the total number of T cells was similar in lungs of iCCR-deficient mice, the number of IAV-specific CD4 but not CD8 T cells in the lung was strongly reduced in the absence of iCCRs. Furthermore, fewer CD4, but not CD8, T cells produced IFN-γ. This CD4 T cell phenotype persisted into the memory stage of infection, with fewer IAV-specific and IFN-γ[SUP]+[/SUP] CD4 but not CD8 T cells at 29 days post infection. In conclusion, despite having limited impact on antigen-presenting cell migration between the lung and the draining lymph node, iCCR deletion is associated with an altered CD4 T cell response to IAV infection.

Keywords: Antigen presentation; Flu; Lung; Mouse; Respiratory inflammation.

 
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