Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury

Wicher, Grzegorz K.Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab (författare)

Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.

Wallenquist, UlrikaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ulwal226 (författare)
Lei, YingKarolinska Inst, Immunol & Allergy Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (författare)
Enoksson, MattiasKarolinska Inst, Immunol & Allergy Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (författare)
Li, XiaofeiKarolinska Institutet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Karolinska Inst, Dept Neurosci, Stockholm, Sweden. (författare)
Fuchs, BarbaraKarolinska Inst, Immunol & Allergy Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (författare)
Abu Hamdeh, SamiUppsala universitet,Neurokirurgi(Swepub:uu)samab670 (författare)
Marklund, NiklasUppsala universitet,Neurokirurgi(Swepub:uu)niklmark (författare)
Hillered, Lars,1952-Uppsala universitet,Neurokirurgi(Swepub:uu)larshill (författare)
Nilsson, GunnarKarolinska Institutet,Uppsala universitet,Hematologi,Karolinska Inst, Immunol & Allergy Unit, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.(Swepub:uu)gunnarns (författare)
Forsberg Nilsson, Karin,1963-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)karifors (författare)
Uppsala universitetNeuroonkologi (creator_code:org_t)

Ingår i:Journal of Neurotrauma: Mary Ann Liebert Inc34:22, s. 3173-31820897-71511557-9042

Av författaren/redakt...: Wicher, Grzegorz ...; Wallenquist, Ulr ...; Lei, Ying; Enoksson, Mattia ...; Li, Xiaofei; Fuchs, Barbara; visa fler...; Abu Hamdeh, Sami; Marklund, Niklas; Hillered, Lars, ...; Nilsson, Gunnar; Forsberg Nilsson ...; visa färre...

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