Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors

Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi) CCR2(+) monocytes can give rise to all m phi subsets in both healthy and inflamed colon and we show that the CX3CR1int pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1 hi m phi. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m phi. Phenotypic analysis of human intestinal m phi indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m phi in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.

Scott, C. L. (författare)
Uronen-Hansson, HeliLund University,Lunds universitet,Slemhinnans immunologi,Forskargrupper vid Lunds universitet,Mucosal Immunology,Lund University Research Groups(Swepub:lu)med-hiu (författare)
Gudjonsson, SigurdurLund University,Lunds universitet,Urologi,Forskargrupper vid Lunds universitet,Urology,Lund University Research Groups(Swepub:lu)urok-sgu (författare)
Jansson, O. (författare)
Grip, OlofLund University,Lunds universitet,Gastroenterologi,Forskargrupper vid Lunds universitet,Gastroenterology,Lund University Research Groups(Swepub:lu)medf-ogr (författare)
Guilliams, M. (författare)
Malissen, B. (författare)
Agace, W. W. (författare)
Mowat, A. Mc I. (författare)
Slemhinnans immunologiForskargrupper vid Lunds universitet (creator_code:org_t)

Av författaren/redakt...: Bain, C. C.; Scott, C. L.; Uronen-Hansson, ...; Gudjonsson, Sigu ...; Jansson, O.; Grip, Olof; visa fler...; Guilliams, M.; Malissen, B.; Agace, W. W.; Mowat, A. Mc I.; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Immunologi inom ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.